| 5.1 |
General Requirements: |
| 5.1.1 |
The quality control laboratory should be designed, constructed and maintained in such a way that it prevents entry for insects and rodents. |
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| 5.1.2 |
The interior surface (walls, floor, and ceilings) should be smooth and free from cracks. |
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| 5.1.3 |
Adequate provision is made for equipment and space to carrying out necessary tests. |
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| 5.1.4 |
Proper air ventilation system should be installed to ensure dust free environment. |
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| 5.1.5 |
The laboratories should have adequate lighting and ventilation facility. |
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| 5.1.6 |
Air-conditioning to be installed to maintain temperature and relative humidity for satisfactory functioning of the laboratory equipments or instruments and that will not adversely affect the accuracy of the testing and storage of drugs. |
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| 5.1.7 |
Acid, alkali and solvent resistant tabletops should be provided and should be smooth and free from crevices. |
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| 5.1.8 |
All staff in the laboratory should possess necessary qualification, proper training and shall have adequate, experience for their assigned duties. |
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| 5.1.9 |
A training record of all the personnel working quality control department should be maintained.
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| 5.1.10 |
All quality related planning should be carried out regularly and organise the quality system audit and follow up action of the corrective actions if any; investigation of technical complaints. |
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| 5.1.11 |
All quality related planning should be carried out regularly and organise the quality system audit and follow up action of the corrective actions if any; investigation of technical complaints. |
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| 5.2 |
Equipment’s: |
| 5.2.1 |
All analytical instruments should be procured as per cGMP requirement and housed in dust-free environment. |
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| 5.2.2 |
Whenever require conditions of temperature and humidity should be maintained with periodic checks. |
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| 5.2.3
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Surrounding areas of the Instruments/Equipments and benches should be kept clean and tidy. |
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| 5.2.4 |
AMC visits shall be carried out for sophisticated instruments. |
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| 5.2.5 |
Record environment monitoring of Quality control department wherever applicable. |
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| 5.2.6 |
Spectra, graphs and additional test records shall be signed by the analyst and attached to the analytical report. |
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| 5.2.7 |
Filter mobile phase/Buffer with 0.45µ filter paper before use. Properly sonicate and degas the mobile phase before use. |
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| 5.2.8 |
Those Instruments required calibration should be calibrated at regular intervals and records of such calibration to be maintained. |
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| 5.2.9 |
The frequency of calibration may differ from instrument to instrument and all Equipment/Instruments records should be maintained. |
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| 5.2.10 |
The records should contain the following :
a) Name of Equipment or Instrument or apparatus.
b) Manufacturer’s name, model number and ID No.
c) Date of receipt, Location and Qualification history.
d) Manual Copy.
e) Frequency of Calibration and Maintenance Frequency.
f) Log Book.
g) Calibration and maintenance status of the equipment.
h) List of authorised users or operators, if any.
i) List of spares and accessories, if any |
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| 5.2.11 |
For most of the equipments and instruments, Standard Operating Procedures for calibration and calibration schedule should be prepared by the laboratory and a logbook should be maintained. |
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| 5.2.12 |
A progress register for non-functional equipments and action for procurement of spares and accessories, monitoring thereof, should be maintained. |
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| 5.2.13 |
A Standard Operating Procedure for preventive maintenance of machine or equipment or apparatus should be available with the laboratory. |
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| 5.2.14 |
Other equipments such as burettes, pipettes, volumetric flasks, weight boxes, thermometers, etc., should have thorough checked for accuracy of calibration before acceptance for use. |
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| 5.2.15 |
Those equipments, instruments giving abnormal results or defective must be labelled as ‘Out of Order’ till they are repaired and after equipments / instrument are repaired they should be recalibrated before use. |
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| 5.2.16 |
Autoclaves must meet the requirements described for operations, safety and validation procedures, and the validation carried out by the laboratory should be recorded. |
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| 5.3 |
Fume Hood Cabinet: |
| 5.3.1 |
Work involving the evolution of harmful and obnoxious vapours should be carried out in a Fume Hood. |
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| 5.3.2 |
The exhaust system of the fume hood should be checked frequently to ensure that it is working in order. |
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| 5.4 |
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| 5.4.1 |
All chemical and reagent receipt, consumption and stock data should be maintained. |
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| 5.4.2 |
All reagents and solutions in the laboratory should be properly identified with a label. |
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| 5.4.3 |
Follow MSDS while handling the chemicals. |
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| 5.4.4 |
Spectra, graphs and additional test records shall be signed by the analyst and attached to the analytical report. |
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| 5.4.5 |
Do not heat organics solvents directly on heating mantle. Use water bath. |
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| 5.4.6 |
Do not use volatile solvents near flame. |
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| 5.4.7 |
The contents of containers where the labels are disfigured or have peeled off must be carefully and thoroughly identified before use or suitably disposed off. |
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| 5.4.8 |
A standardisation register should be maintained along with its raw data for all standard solutions and volumetric solutions.
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| 5.4.9 |
Standard Operating Procedure for preparation and standardisation on stock solutions, for all standard solutions, volumetric solutions must be available for the guidance of staff. |
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| 5.4.10 |
All bottles, Containers of stock solutions and of standard solutions should bear the following details:
1. Name of solution
2. Strength
3. Date of preparation
4. Validity period/Use before date, (Based on the stability of the solution)
5. Prepared by
6. Checked by |
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| 5.4.11 |
All Volumetric Solutions should be re-standardized at defined interval. |
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| 5.4.12 |
Volumetric solutions, Stock solutions should be discarded immediately if any sedimentation in observed irrespective of declared shelf life. |
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| 5.4.13 |
To avoid contamination of chemicals and reagents special care must be taken with standard solutions. |
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| 5.4.14 |
Quantities of such solutions in excess of requirements should not be returned to stock bottles but should be discarded. |
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| 5.4.15 |
After the use of a reagent, place the bottle at its right place on the shelf in such a way that the label is clearly visible and is in front. |
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| 5.4.16 |
Before putting the bottles back on the shelf wipe the bottle in case some reagent/liquid is spilled down the sides. |
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| 5.4.17 |
In-compatible chemicals should be stored away from each another at specified storage container and conditions. |
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| 5.4.18 |
Do not accumulate chemicals/ reagents / glassware /equipments on benches or in fume cupboards. |
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| 5.4.19 |
After use always return all chemicals/ reagents / glassware /equipments to their designated places. |
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| 5.4.20 |
Heavy containers and bottles of dangerous chemicals should be returned to main chemical store as soon as possible. |
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| 5.4.21 |
When chemicals are transferred from big containers to small bottles for regular use they should be properly marked with all details of the original container. |
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| 5.4.22 |
Any bottle containing chemical that need to be carried a short distance should be supported at the base and neck. |
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| 5.4.23 |
For carrying to longer distances use the special carriers, which are available. |
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| 5.4.24 |
The transfer of solvents and hazardous chemical from bulk containers should be done carefully and with proper device funnels, pumps etc. |
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| 5.5 |
Good Housekeeping, Hygiene Safety: |
| 5.5.1 |
All personnel working and entering in Quality Control Department should follow entry and exit procedure. |
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| 5.5.2 |
General and specific written down instructions for safety shall be circulated to each staff member and the instructions be revised periodically as appropriate. |
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| 5.5.3 |
Standard Operating Procedure for safety, house-keeping should be prepared in accordance with the various rules and regulations of the Government of India and include the following requirements. |
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| 5.5.4 |
Drinking, eating and smoking shall not be permitted in the laboratories. |
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| 5.5.5 |
Food for human consumption should be prohibited in working or storage areas. |
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| 5.5.6 |
Safety data sheets must be made available to staff before testing is carried out. |
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| 5.5.7 |
Staff must wear laboratory coats or other protective clothing including gloves and face masks and eye protection wherever required. |
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| 5.5.8 |
The staff must be educated in the first aid techniques, emergency care. |
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| 5.5.9 |
The laboratories should have adequate first aid kit and fire fighting equipments located at the right places. |
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| 5.5.10 |
Any person found suffering from illness which may adversely affect the quality and integrity of testing shall be excluded from direct contact with test system. |
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| 5.5.11 |
All the staff must be familiar and trained with the use of fire fighting equipment including fire extinguishers, fire blankets and gas masks. |
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| 5.5.12 |
Microbiologist carrying out sterility tests should wear sterilised garments including headgear, face masks and shoes. |
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| 5.5.13 |
Appropriate facilities for the collection, storage, and disposal of wastes should be made available. |
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| 5.6 |
Reference Materials : |
| 5.6.1 |
Reference materials are necessary for the testing and, or calibration, validation or verification of a sample or of equipment, instruments or other devices and all such materials should be avail from agency authorised by Government of India or any other International body. |
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| 5.6.2 |
The laboratory should prepare working standard by comparing with the reference standards and should be routinely checked for their purity by selecting parameters such as identity, loss on drying or on water, impurity and assay, etc. |
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| 5.6.3 |
Whenever, any new reference material is received by the laboratory, a code number should be assigned and this code number shall be quoted on the laboratory note book and analytical work sheet. |
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| 5.6.4 |
All working standard should have identification code. |
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| 5.6.5 |
A register pertaining to reference and working standards must be maintained by the laboratory. The following details shall be mentioned in the register:
(i) Source of supply
(ii) Code number of the reference material
(iii) Date of receipt
(iv) Batch number or identification number of the supplying agency
(v) Details like assay value, water content or any other information provided
(vi) Storage condition of the material
(vii) Date of expiry, if any and date of manufacturing if possible. |
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| 5.6.6 |
All working standards should be checked at appropriate intervals or before use to ensure that it has not deteriorated or decomposed during storage. |
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| 5.6.7 |
These observations should be recorded in a register. |
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| 5.6.8 |
All the reference and working standards shall be stored at appropriate storage condition. |
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| 5.6.9 |
Those require storage between 2-8º C should be stored in a refrigerator. |
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| 5.6.10 |
Wherever recommended the material should not be allowed to be frozen. |
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| 5.7 |
Microbiological Cultures: |
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| 5.7.1 |
Standard Operating Procedure for maintenance of microbial culture and sub-culture must be prepared by the laboratories |
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| 5.7.2 |
If the cultures have become non-viable or mutant, proper procedure should be followed to destroy these cultures by autoclaving under authorised personnel for biological testing. |
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| 5.7.3 |
Preferably not more than five passages may be prepared. |
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| 5.7.4 |
All activities be carried out in a aseptic area by authorised person. |
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| 5.7.5 |
The laboratories should perform standard biochemical tests on the sub-culture as given in literature to ensure their viability.
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| 5.8 |
Quality system: |
| 5.8.1 |
The quality system should be designed to ensure the following objectives.
a) The measurements and calibrations should fully conform to the compendia requirements and the methods demonstrably based on validation protocols are followed.
b) It should be effective in providing necessary assurance that the activities or processes or techniques or practices comply with planned arrangements.
c) It helps in early detection and correction of non conformities.
d) Remedial action on the observations by internal and external audits is taken appropriately.
e) It should have a documented quality policy for the organisation. |
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Internal quality system audits: |
| 5.8.2 |
Internal audits are done to assure the integrity of the analysis and such audits should be conducted periodically with a predetermined schedule procedure with appropriate checklist. |
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| 5.8.3 |
Verify that the operations continue to comply with the requirements of quality system and requirements of regulatory authorities. |
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| 5.8.4 |
Internal quality audits shall be carried out by trained and qualified personnel who are independent of the activity to be audited. |
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| 5.8.5 |
The periodicity of quality audit should be fixed by the Head of the laboratory so that each activity is audited at least once in a year. |
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| 5.8.6 |
Head of the laboratory will be responsible for initiation of the corrective action arising from audits and verification of corrective action. |
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| 5.8.7 |
a) Whenever any non-compliance or any diversion is noticed by the team in implementing quality policy or quality system, protocols, the same will be attended by the Quality Manager. |
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| 5.8.8 |
The problem will be analysed and necessary actions will be taken with proper documentation. |
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| 5.8.9 |
The Quality Manager should maintain all the records of the analysis being conducted which includes test system, the type of analysis, date on which analysis is done, etc. |
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| 5.8.10 |
Quality Manager should also maintain copies of all protocols pertaining to different activities being checked by the audit team.
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| 5.9 |
Management review: |
| 5.9.1 |
Quality system reviews should be conducted by the top management at least once in every twelve months and the agenda of review should generally cover the following:
a) Report or input of internal audits
b) Matter arising from previous reviews
c) Report of external audits, if any
d) Surveillance report, if any
e) Result of proficiency testing
f) Complaints or feedback received from users of laboratory services
g) Details of in-house quality control checks
h) Need of amendment of the quality system and documentation
i) Induction training of new staff
j) Any other requirements of the laboratory. |
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| 5.10 |
Standard Operating Procedures: |
| 5.10.1 |
Standard Operating Procedures are written procedures for different activities being conducted in a laboratory and should include the following characteristics:
a) They shall be written in a chronological order listing different steps leading to an analysis of drugs or calibration of an instrument.
b) Testing laboratories should have Standard Operative Procedure manuals and have its periodic review.
c) It should be user friendly documents and should include designation of the person responsible for intended activity. |
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| 5.10.2 |
Standard Operating Procedures in addition to those recommended under various activities should also be prepared to the minimum in respect of the following:
a) Sample handling and accountability.
b) Receipt identification, storage, mixing and method sampling of the test and control articles.
c) Record keeping, reporting, storage and retrieval of data.
d) Coding of different studies, handling of data including use of computerized data system.
e) Operation of technical audit personnel in performing and reporting audits, inspections and final report reviews.
f) Routine inspection of cleaning, maintenance, testing, calibration and
g) Standardisation of instruments.
h) Action to be taken in respect of equipment failure.
i) Analytical data methods.
j) The raw data.
k) Data handling and storage retrieval.
l) Health and safety protection.
m) Storage and maintenance of microbial cultures.
n) Use and storage of reference standards.
o) Monitoring of testing of samples.
p) Method of retention of unexpended samples, their location, maintenance and disposal.
q) Document control.
r) Technical complaints.
s) House-keeping.
t) Corrective and preventing action.
u) Working procedure (test methods).
v) Calibration Manual.
w) Training manual. |
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| 5.11 |
Protocols and specifications archive: |
| 5.11.1 |
Every laboratory should have a specification archive and current versions of all necessary specifications should be kept as per the requirements of the Act and the rules made there under. |
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| 5.11.2 |
All updates and corrections must be noted from updated volumes of Pharmacopoeias to prevent the use of obsolete sections. Supplements and addendum should also be made available in the laboratory. |
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| 5.11.3 |
The specification archive should contain the following :
a) List of all the pharmacopoeias;
b) A file on patent and proprietary medicines (non-Pharmacopoeial) test methods to specifications prepared and validated by the manufacturer or by the laboratory itself.
c) The test methods should be submitted to the concerned Drug Control
Authority.
d) The validated test methods developed by the manufacturer or the
laboratory should stand to the requirements of compendial parameters in regard to its precision, accuracy, reproducibility, specificity, linearity, and ruggedness etc. |
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| 5.12 |
Raw data: |
| 5.12.1 |
Raw data refers to the laboratory work sheet, note books or analysis sheet,
Records, memorandum, notes or extract copies thereof that may be the results of general observations and other activities. |
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| 5.12.2 |
Such raw data shall include hand written notes, photographs, software, drawings, computer printouts, spectral charts, dictated observations or recorded data from automated equipments. |
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| 5.12.3 |
The raw data also includes record of environmental monitoring, calibration, records of equipments, integrator output from analytical equipment, including work-sheet used to read note information from Light Emitting Diode (LED) display of any equipment. |
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| 5.12.4 |
A single line shall strike through the data being changed; the correct information shall be recorded along with the old data and the reason of change. |
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| 5.12.5 |
The analyst making the change shall be identified by his signature with date. |
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| 5.12.6 |
In case of automated data collection system, the person responsible shall be identified at the time of data output. |
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| 5.12.7 |
The original entry must be saved and the systems have audit trial for all the data. |
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| 5.12.8 |
Data integrity and security shall be maintained and the data shall not be accessible to any unauthorised person. |
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| 5.13 |
Storage and archival: |
| 5.13.1 |
The residual sample shall be retained in proper storage condition for a period of one year after the final report. |
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| 5.13.2 |
The laboratory must establish and maintain procedures for the identification collection, indexing, retrieval, storage, maintenance, and disposal of all quality documents. |
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| 5.13.3 |
All the raw data, documentation, Standard Operative Procedures, protocols, and final reports are to be retained and there should be archives for orderly storage and retrieval of all raw data, documentation, protocols, interim and final report.
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| 5.13.4 |
The archive should provide a suitable environment that will prevent modification, damage, or deterioration and/or loss expeditious. |
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| 5.13.5 |
The condition under which the original documents are stored must ensure their security and confidentiality. |
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| 5.13.6 |
Paper documents shall not be kept for long periods under high humidity and raw data in the form of tape and discs are to be preserved with care. |
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| 5.13.7 |
In case of storage of only optical disc, the life of disc should be longer than the storage time. |
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| 5.13.8 |
Raw data on thermal paper might fade away with time; therefore, a photocopy of the thermal paper shall also be retained in the archive. |
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| 5.13.9 |
Time for which records are retained shall be prescribed in the documents. |
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