1. GMP for Process Development Facilities
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2. cGMP Facility Equipments
Laboratory, Upstream and Downstream Equipments
Formulation and Filling Equipments
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3. Ǿ 211.63 Equipment design, size and location
Equipment used in the manufacture, processing, packing or holding of a drug product shall be of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance
Effectiveness of Equipment = Product Quality
Equipment value = Part in your assess
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4. Equipment: General Requirement
Operating criteria are adequate for the process (size, speed, effectiveness)
Availability of spare and servicing (GLOCAL!!)
Maintenance: ease of maintenance, frequency, ease of disassembly and reassembly
Environmental issue: dust/noise production, utility consumption (electricity, water, steam, air)
Construction material and Design (Ǿ211.65)
Availability of process control for main parameters and connectability to SCADA system for the main supervisory computer system and ability to work in cascade to other equipments
Cost: base price and other direct and indirect costs, points (2, 3) other cost for validation files
Availability of design and detailed maintenance manuals. Guidelines and manuals for qualifications, maintenance and validation program.
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5. Ǿ 211.65 Equipment construction
Equipment shall be constructed so that surfaces that contact 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 beyond that official or other established requirements.
The manufacturer should determine which materials are to be processed in the equipment and where contact between materials and machinery occurs.
Grade of glass or stainless steel used in each part of the equipment (eg: distilled water is very corrosive. The stainless steel used usually 316L passivated with 15-30% nitric acid.
Any reaction between materials and equipment is undesirable and will reflect on the chemical and physical characteristics of the final product
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6. Ǿ 211.65 Equipment construction
Any substances 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 establish requirements.
This have direct relation with the design, construction, and placement of manufacturing equipment.
Motors, drive belts, gears and other potential sources of lubricants contamination should be located away from any part in contact with the products (eg: vessel, dispensers, etc)
Lubricants should be usually monitored and MUST be of FOOD GRADE (GRAS code)
Gaskets and O-rings should be monitored to ensure not break down which cause both external contamination as well as internal contamination. (gaskets and O-ring particles contaminating the materials). BOTH gaskets and O-ring MUST be of FOOD GRADE (GRASS code)
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7. Ǿ 211.67 Equipment cleaning and maintenance
Equipment and utensils shall be cleaned, maintained and sanitized at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality or purity of the drug product beyond the official or other established requirements.
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8. Ǿ 211.67 Equipment cleaning and maintenance (cont)
Written procedures shall be established and followed, including utensils, used in the manufacture, processing, packing or holding of a drug products. These procedure shall include, but not necessarily limited to, the following:
Assignment of responsibility for cleaning and maintaining equipment
Maintenance and cleaning schedule, including, where appropriate, sanitizing schedule
A description in sufficient detail of the methods, equipment and material used in cleaning and maintenance operations, and the methods of disassembling and reassembling equipment as necessary to assure proper cleaning and maintenance.
Removal of obliteration of previous batch identification
Protection of clean equipment from contamination prior to use.
Inspection of equipment for cleanliness immediately before use
Records shall be kept of maintenance, cleaning, sanitizing and inspection as specified in and
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9. The regulation require written procedures for cleaning, maintenance and sanitation plan.
Engineering department approve the maintenance plan, where QC approve cleaning and sanitation
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10. FDA Guidelines of Validation of Cleaning Procedures
Availability of approved validation protocol
Approved validation reports
Equipment design and cleanability
Define, appropriate cleaning SOP to address difficult cleaning areas
Time scales between use and cleaning and between cleaning and re-use
Operator training
Specificity and sensitivity of analytical methods
Sampling methods (swab test, solvent rinse, placebo flush as lactose flush for solid mixing machines, visual examination)
Acceptable residue limit (some guidelines accept from 1/100 to 1/1000 of the minimum therapeutic dose)
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11. Automatic, mechanical and electrical equipmentǾ
Automatic, mechanical and electrical equipment
Automatic, mechanical, or electrical equipment or other types of equipment, including computers, or related systems that will perform a function satisfactory, may be used in the manufacture, processing, packing and holding of a drug product. If such equipment is so used, it shall be routinely calibrated, inspected or checked according to a written program designed to assure proper performance. Written records of those calibration checks and inspections shall be maintained.
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12. Automatic, mechanical and electrical equipment (cont)Ǿ
Automatic, mechanical and electrical equipment (cont)
Appropriate controls shall be exercised over computer or related systems to assure that changes in master production and control records or other records are instituted only by authorized personnel, input and output from the computer or related systems of formulas or other records or data shall be checked for accuracy
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the degree and frequency of input/output verification shall be based on the complexity and reliability of the computer or related system
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13. Automatic, mechanical and electrical equipment (cont)Ǿ
Automatic, mechanical and electrical equipment (cont)
A backup file or data entered into the computer or related system shall be maintained except where certain data such as calculations performed in connection with laboratory analysis, are eliminated by computerization or other automated process. In such instances a written record of the program shall be maintained along with appropriate validation data.
Hard copy or alternative system, such as duplicates tapes, or microfilm, designed to assure that backup data are exact and complete and that it is secure from alteration, inadvertent erasures, or loss shall be maintained.
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14. Equipment of the platforms (remember)
Validated equipments (IQ, OQ), working under cGMP (standard version is preferred unless special design is required)
Cleanable (no dead point), easy to clean with CIP system
Sterilizable (all components and connections can stand steam for sterilization)
Flexible for upgradability, multipurpose design, easy to maintain
Able to connect with SCADA system
Easy to operate as ease as possible
Easy to maintain either by local engineers (maintenance and calibration contract)
Environment friendly with minimal power consumption (ECO version)
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15. Laboratory Equipments (QC, QA, etc) Inclusion Bodies Separation
Utilities Equipments
Laboratory Equipments (QC, QA, etc)
Production Equipment
Preparation Lab
Fermentation
Cell separation
Refolding
Inclusion Bodies Separation
Cell breaking
Purification
Vial filling
Lyophilization
Labeling
Packing
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16. Utilities Equipments Water tanks Water station (tap water quality)
Steam generator
Chiller
Air compressor
Distilled water Unit
Deionized water unit
WFI unit
Oxygen station
Nitrogen station
Carbon dioxide station
Killing tank (liquid waste decontamination system)
Crushing autoclave (solid waste decontamination system)
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17. Steam generator Full material certification
FDA / USP class VI approved material certification
Surface finish certification
Welding procedures and qualifications
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18. Laminar air flow IQ and OQ documentation (cGMP version)
Biological safety class
construction material of bench place
Validated cleaning procedure
Type of HEPA filter and validation
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19. Upstream Equipments (Bioreactor)
utility consumption
construction materials
Welding quality
piping and valve quality
SIP and CIP
Cooling / heating efficiency
computer control system (Validated)
Safety
mechanical seal and ports design
mixing efficiency
MANY MORE!!
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20. Interferon production process design
Freezer
LAF
Incubator
Fermentor
Cell separator
Cell breaking
Inclusion Body separation
refolding
purification
Vial filling
Lyophilization
Labeling
Packing
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21. Autoclave Steam Sterilizer – Fully Automatic
• Double body construction, single chamber for steam and water, covered externally by outer shell. • Lid made of thick stainless steel, pressure up to 22 PSI factory set at 15 PSI. • Complete unit with automatic air purging, Digital Temperature control & Indication with 0.1°c  Accuracy/ Resolution, with electronic Digital timer range 0 to 99 min. • Autoclaving time cycle automatically starts when set pressure is achieved. • Automatic steam release once autoclaving cycle complete. • Complete with pressure gauge, safety valve, steam release valve, extra safety valve. • Incorporated with an Automatic Pressure Control Switch as an additional safety device. • Low Water level cut-off : Low water level cut-off assembly connected to heater which automatically cuts off power to heater if water level is not sufficient thus eliminating heater burn outs. • Foot lifting arrangement included for Capacity 125 Ltr. and above. Not included/required for lower sizes. •  Provided with S.S. L-304 grade perforated basket. • Unit works on 230 V Ac, 50 Hz.
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22. Inner body made of heavy gauge Stainless Steel LM-
STANDARD MODEL  :   
HIPL-001 B
GMP MODEL  : 
HIPL-001 C
Inner body made of heavy
gauge Stainless Steel LM-
304 grade with argon
welded joints, outer body
made of S.S. LM-304 grade
mirror finished.
gauge Stainless Steel LM
316 grade with argon
made of SS LM-304
grade mirror finished
Provided with Validation
Documents.
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