Friday, April 3, 2009

Performance Qualifications:

Production Area:
1- The production premises or area should be preferably laid down in such a way as to allow the production to take place in areas connected in a logical order corresponding to the sequence of the operation and to the requestic cleanliness level. The GMP rule states that the space for each process must be adequate.
2- The adequacy of the working and in process storage space should permit the orderly and logical positioning of equipment and materials so as to minimize the risk of confusion between different medicinal products or their components, to avoid cross contamination and to minimize the risk of emission or wrong application of any of the manufacturing or control steps.
3- Where starting and primary packaging materials, intermediate or bulk products are exposed to the environment, interior surfaces (walls, floors and ceilings ) should be smooth, free from cracks and open joints, and should not shed particulate matter and should permit easy and effective cleaning and if necessary, disinfection.

D Equipments

Production Equipment:
The quality of the product starts from the design stage of the equipment (other factors are also involved), so the equipment used for the production should have
1- Suitable size, design and location (the validility of the suitability of the size should be done and record must be present.
2- The production equipment must be automatic (preferably) and design must be that it saves energy, time, labour and provide quality product.
Syrup Section:
Purified Water:
The de ionizer plant should be automatic and in separate room with the signs of water flow valve operations direction, procedure, installation validations, performance qualification, operational qualifications. The Incharge of de ionizer must have the record of number of re generation, the quantity of solutions used for cation and anion charging as the manual operations increase in wastage of time, wastage of solutions, leakages, increase in labour use and overtime etc. while the atomization save the above factors. Atomization is an important part of GMP.
Syrup Filling Machine:
The syrup filling machine should be automatic with the digital controls of volume setting with the filling increase or decrease adjustments. Capping and Sealing machine must be automatic.
Quarantine Area:
Syrup section must have quarantine area where the batch after filling may be kept till the release or till receiving the release from quality control department.
Washing Area:
The syrup section have not washing area with adequate space.
Air System:
The air of syrup section must be replaced 20 times within an hour and it must have the particle count NMT 10,000 counts.
Syrup Cooking Tank:
i) It must have digital temperature sense probe, temperature recorder, the temperature sense record probe must be connected with the steam shut and on valve, so that during the manufacturing procedure the temperature must be controlled, presently we are measuring the temperature with thermometer and in case of increase of temperature we have no cooling line so that the temperature can be brought down at the required level, if we have automatic system with the syrup cooking tang we can save time, energy, labour and better quality of product.
ii) The mixing motor must have speed controller.
iii) Transfer of syrup
Batch Processing Records:
Before any processing begins, there should be recorded checks that the equipment and work station are clear of previous products, documents or materials not required for the planned process, and that equipment is clean and suitable for use.
During processing, the following information should be recorded at the time each action is taken and, after completion, the record should be dated and signed in agreement by the person responsible for the processing operations:
a) the name of the product;
b) dates and times of commencement, of significant intermediate stages and of completion of production;
c) name of the person responsible for each stage of production;
d) initials of the operator of different significant steps of production and, where appropriate, of the person who checked each of these operations (e.g. weighing);
e) the batch number and/or analytical control number as well as the quantities of each starting material actually weighed (including the batch number and amount of any recovered or reprocessed material added);
f) any relevant processing operation or event and major equipment used;
g) a record of the in-process controls and the initials of the person(s) carrying then out, and the results obtained;
h) the product yield obtained at different and pertinent stages of manufacture;
i) notes on special problems including details, with signed authorization for any deviation from the manufacturing formula and processing instructions.

Batch Packing Records:
Before any packaging record should be recorded checks that the equipment and work station are clear of previous products, documents or materials not required for the planned packaging operations, and that equipment is clean and suitable for use. The following information should be entered at the time each action is taken and, after completion, the record should be dated and signed in agreement by the person(s) responsible for the packaging operations:
a) the name of the product;
b) the dates(s) and times of the packaging operations;
c) the name of the responsible person carrying out the packaging operation;
d) the initials of the operators of the different significant steps;
e) records of checks for identity and conformity with the packaging instructions including the results of in-process controls;
f) details of the packaging operations carried out, including references to equipment and the packaging lines used;
g) whenever possible, samples of printed packaging materials used, including specimens of the batch coding, expiry dating and any additional overprintin;
h) notes on any special problems or unusual events including details, with signed authorization for any deviation from the manufacturing formula and processing instructions;
i) the quantities and reference number or identification of all printed packaging materials and bulk product issued, used, destroyed or retuned to stock and the quantities of obtained product, in order to provide for an adequate reconciliation.
àTo safe energy, fuel, timing, labour the boiler must have automatic firing system which corresponds to steam pressure maximum and minimum.
àRecorder for operation timing
àUse of de ionized water (quantities required starting boiler before operation, during operation) these quantities must be validated
àSafety Operation (setting of safety valve limits and their check this should be done 2 to 3 times within a year)
àWritten procedure of boiler operation
àThe area of the boiler installation must be clean walls and floors should be smooth and free of oily substances.
àThe blow down quantities, analysis records must be present.
àThe record of total dissolved solid must be present.
àThe record of boiler inspection from the govt. official must be present with comments.
There are three types of steam
i) Wet Steam (Steam with moisture content)
ii) Dry Steam
iii) Clean Steam
àIn syrup section the wet steam is used there are some specifications of the wet steam. There is the limit of water contents in the steam above which goes into loss of increase of heating timing.
àThe steam in syrup section has no direct contact with the product so the installations for the steam rout is of non toxic materials is more better
the following three points must be validated, the validation should be done by the quality assurance department with the help of maintenance department and quality control.
i) Installation qualifications (IQ)
ii) Operational qualifications (OQ)
iii) Performance qualifications (PQ)
iv) Design Qualification (DQ)
( This is a part of master plan validations )
for validations see master plan validations
Note: the maintenance department should have complete design, layout and layout of piping, valves, traps, heat exchangers their calibrations, validations and records
Steam Cattle:
The steam cattle must be calibrated and validated, temperature readable capacity, temperature sensor and certificate from the manufacturer that the material used is pharmaceutical or food grade. The surfaces must be smooth inside and free of scratches.
Suspension Preparation Tank:
The suspension tank must be validated and calibrated, the silver san should be automatic up and down movement controller for the speed of silver san. The valves must have numbered and direction of operation.
Syrup Distributions Tank:
There should be complete design and layout and certification from the manufacturer about the material used for the construction of tank that the material used is of pharmaceutical or food grade and non reactive with the direct contents and motor has speed controller and must meet the required specifications.
Storage Tank:
The storage tank have temperature sensing probes, digital meters and a cool water circulation line.
Filtration Pump:
There should be Filter Press pump, the filter sieves should be S S, non reactive, non corrosive materials.
The procedure for the filtration must be present, safety parameters and must be validated. The filters used must not be of sheets and they should not give fibers.
Facilities in Syrup Section:
Compressed Air
The compressor should be installed in an dust and smoke free area, for better performance the walls should be finished and floor should be made of chips.
The compressed air should be cleaned by installing moisture separator or de humidly fires and the installation should be validated which should be described in master plan of validations.
1- Equipment shall be constructed so that surfaces that contact with drug components, in process materials, or drug products shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements.
2- Any substance required for operation, such as lubricants or coolants, shall not come into contact with components, drug product containers, closures, in process materials, or drug products so as to alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements.
3- A certificate for the non toxicity, non absorptive property, smooth surfaces, non reactive materials have been used naming the grade of the material should be present supplied from the manufacturer.

Equipment Maintenance and Cleaning:
Written procedures shall be established and followed for cleaning and maintenance of equipment, including utensils, used in the manufacture, processing, packing, or holding of a drug product. These procedures shall include, but are not necessarily limited to, the following:
1- Assignment of responsibility
2- A description in sufficient detail of the methods, equipment, and materials used in cleaning and maintenance operations, and the methods of disassembling and reassembling equipment as necessary to assure proper cleaning and maintenance;
3- The references should be present for the use of automatic equipments their validations, their calibrations or if computers are used in manufacturing processes for input or output controls they should be validated and calibrated, checks should made according to a written program, design to assure proper performance, appropriate controls shall be exercise over computer or related systems to sure that changes in master production and control records or other record are instituted only by authorized persons (deviation form should be filled )
Control of Drug Containers and Closures:
Written procedures must be present that describes the receipt identification, storage, handling, sampling, testing, approval and rejection of components.
1- Upon receipt and before acceptance, each container or grouping of containers of components, drug product containers, and closures shall be examined visually for appropriate labeling as to contents, container damage or broken seals, and contamination.
2- Components, drug product containers, and closures shall be stored under quarantine in identified areas until they have been tested or examined, as appropriate, and released. Storage within the area shall conform to the requirement.
3- Each lot of components, drug product containers, and closures shall be withheld from use until the lot has been sampled, tested, or examined, as appropriate, and released for use by the quality control unit.
4- The containers of components selected shall be cleaned where necessary, by appropriate means.
5- The containers shall be opened, sampled, and released in a manner designed to prevent contamination of their contents and contamination of other components, drug product containers, or closures.
6- If it is necessary to sample a component from the top, middle and bottom of its container, such sample subdivisions shall not be composite for testing.Sample containers shall be identified so that the following information can be determined: name of the material sampled, the lot number, the container from which the sample was taken, the date on which the sample was taken, and the name of the person who collected the sample

No comments: