FACILITY VALIDATION

1.0 Purpose:

The purpose of this document is to qualify new facility, in order to establish documented evidence that the facility has been designed and installed as per the approved design specifications, made operational, perform as intended and meets the requirements of national and international requirements/ guidelines for c GMP`s, safety and environment.

2.0 Reason for Establishing protocol for qualification of the facility:

Facility has been designed and constructed to facilitate manufacturing and packing of tablets, hard gelatin capsule and dry syrups formulations at Bommasandra Industrial area. Hence qualification of the facility is planned.

3.0 PROTOCOL APPROVAL SIGNATURES

4.0 Scope:

This protocol is applicable for qualification of the facility of Micro labs limited, Bommasandra, Bangalore.

5.0 Validation team and responsibilities:

Engineering Department: Execution, compilation and review of data

Quality Assurance : Preparation, review and approval of the protocol

Production : Checks and Review

Quality control : Execution of the protocol.

6.0 Design Qualification (DQ):

6.1 Purpose:

The Purpose of design qualification is to ensure that all the critical aspects of cGMP’s, Product/Process requirements, safety, environment, ergonomics, statutory requirements and environment

controls have been considered in designing the new facility and the same has been complied & documented

6.2 Facility Design in brief:

Ground floor: Raw material store, Packing material store, tablet manufacturing area, capsule manufacturing area, dry syrup manufacturing area, primary packing cubicle, bulk storage area, secondary packing area, Finished goods store, washrooms, change rooms (Primary and secondary), cleaned equipment storage area, Dispensing area, purified water plant.

First floor : Quality control laboratory, Quality assurance

Service floor: Air handling systems/ utilities

7.0 Critical Attributes to be met while designing the facility:

7.1 Layout and Design must aim to minimize the risk of errors and permit effective cleaning and maintenance in order to avoid cross contamination, build up of dust or dirt and in general any adverse effect on the quality of products.

7.2 Location and surroundings:

All Measures to be considered in order to avoid risk of contamination from external environment which includes open sewage, drain, public lavatory or any factory which produces disagreeable or obnoxious odor, fumes, excessive soot, dust, smoke or chemical emissions.

7.3 Premises:

Premises shall be designed & equipped so as to afford maximum protection against the entry of rodents, crawling insects, flying insects, lizards, flies, birds & other animals.

7.3.1 The premises shall be provided with adequate working space to allow orderly & logical placement of equipments.

7.3.2 Movement of materials and personnel shall be considered while designing the facility so as to avoid any risk of mix-up, avoid possibilities of contamination, cross contamination & crisscross movements.

7.3.3 Lighting shall be given due importance in all areas within & outside the facility so as to carryout various operations with ease & comfort. Emergency lights shall be provided in corridors, process areas, Stores, packaging areas and stairs.

7.3.4 Drain pits shall be designed to prevent back flow, wherever drainage is provided, the same shall be concealed.

7.3.5 Air handling systems shall be designated to provide class 100,000 at rest in areas where product is directly exposed to environment. Air handling systems shall be dedicated to avoid possibilities of cross contamination.

7.3.6 Wood shall not be used anywhere in the production and storing area.

7.3.7 Anti-Termite treatment shall be carried out below the floor bed, flagging concrete around the building and walls within the facility.

7.3.8 Adequate areas shall be designated to allow sufficient and orderly warehousing of various categories of materials and products like starting ( raw materials ) and packing materials, intermediates, bulk and finished products, products in quarantine, released, rejected, returned or recalled.

7.3.9 Temperature & related humidity controls shall be provided for storage of empty & filled capsules. Areas for processing of capsule formulations shall also be temperature & relative humidity controlled.

7.3.10 Receiving & despatch bays shall protect materials & products from adverse weather conditions.

7.3.11 Various areas in the stores shall be clearly segregated. Any system replacing physical quarantine shall give equivalent assurance of segregation.

7.3.12 There shall be separate sampling area in the Stores with class 100,000 environment reverse LAF.

7.3.13 Segregation shall be provided for storage of rejected, recalled or returned materials or products.

7.3.14 Separate, safe & secured area shall be provided for printed packaging materials.

7.3.15 Dispensing area(s) with class 100,000 environment & reverse LAF shall be provided.

7.3.16 Production areas shall be designed to allow the production in uni-flow with logical sequence of operations.

7.3.17 Working & in process space shall be adequate to permit orderly & logical positioning of equipments & man-material movements.

7.3.18 Electrical fittings, pipe work, ventilation openings & service lines shall be designed, fixed and constructed to avoid creation of recesses. They shall be concealed. Service lines shall be identified by colors & the nature of supply & the direction of flow shall be marked/indicated.

7.3.19 Primary & secondary change rooms for gowning/degowning shall be provided.

7.3.20 Toilets shall be separate for males & females. Toilets shall not be directly connected with production or storage areas.

7.3.21 Quality control laboratory shall be independent from the production areas. Separate areas shall be provided each for physico-chemical, microbiological, instruments and packing materials testing.

7.3.22 Modular furniture shall be provided in Quality Control laboratory.

7.3.23 Sufficient & suitable storage space shall be provided for test samples, retained samples, reference standards, records etc.

7.3.24 Separate AHU shall be provided for microbiological laboratory.

7.3.25 Laboratory shall be provided with potable water & purified water for cleaning and analysis purposes.

7.3.26 Microbiological section shall have arrangements such as air locks & laminar airflow workstation.

7.3.27 Packaging lines shall be independent & adequately segregated.

7.3.28 Lighting in each area of the facility shall be adequate enough to perform activities with ease and comfort.

7.3.29 Lighting fixtures shall be of clean room type.

7.3.30 Dust extraction system to be considered in process area where generation of powder dust is expected during processing.

7.4 Floor:

7.4.1 The floor shall be hard, smooth, non-porous, washable, continuous, chip resistant and durable. There shall be no crevices, cracks or open joints in the floor, epoxy floor shall be considered in areas where product is exposed .

7.4.2 Floor to wall joint shall be coved.

7.4.3 Material used for flooring shall permit easy cleaning and shall not shred any particulate matter.

7.4.4 Vitrified tiles shall be used in toilets, in quality control laboratory and in Quality assurance.

7.5 Walls:

7.5.1 The external walls shall be cement plastered, made with table-molded bricks .

7.5.2 The internal partition walls shall be made with cement concrete blocks, cement plastered and painted to smooth finish, anti-static, anti-fungal and avoid flaking.

7.5.3 Internal walls shall be non-porous, smooth and washable. Corners shall be rounded, no crevices or recesses or protrusions or joints, chip resistant and minimum seams.

7.6 Ceiling:

7.6.1 The ceiling shall be hard, non porous, smooth, cleanable and chip resistant.

7.6.2 False ceiling wherever considered shall be made up of Gypsum Board, painted with polyurethane paint / Emulsion paint.

7.6.3 The wall to ceiling joints shall be coved.

7.7 Paint:

7.7.1 Polyurethane / Emulsion paint over the primer.

7.8 Doors and View panels:

7.8.1 The doors shall be non-porous, smooth, cleanable and flushed with its view panel.

7.8.2 The doors shall be polyurethane coated.

7.8.3 Double glass sealed view panels.

7.8.4 Doors shall open on the same side of the airflow.

7.9 Utilities to be provided:

7.9.1 Air handling units ( Re-circulatory, once through and ventilation).

7.9.2 Purified water system with distribution network in the form of loop.

7.9.3 Compressed air system with distribution network.

7.9.4 Steam

7.9.5 Chilled water

7.9.6 Effluent treatment plant

7.9.7 Power generator backup

7.9.8 Dust extractors in areas where powder dust is generated.

7.10 Electrical requirements:

7.10.1 Single phase & three phase electrical points shall be provided in the facility as per design requirements.

7.10.2 Critical areas and critical equipments shall have back up system in the event of power failure.

7.10.3 Earthling shall be provided to all the points.

7.10.4 Electric wiring shall be concealed.

Flame proof wherever required to be provided.

7.10.5 The lighting units are scientifically apportioned so as to provide adequate light

for the area in which they are used.

7.10.6 Light fixtures shall be accessible to allow proper maintenance, cleaning & to prevent accumulation of dust or foreign matter.

7.11 Safety aspects:

7.11.1 Emergency exits

7.11.2 Smoke detectors

7.11.3 Fire extinguishers.

7.11.4 Easy access to first aid kit.

7.11.5 Camera system.

7.11.6 Solvent storage complying the local statutory regulations.

7.11.7 Round the clock security for the premises

7.12 Regulatory Requirements

(Necessary approvals shall be obtained from following government agencies)

7.12.1 Industrial development corporation, Karnataka.

7.12.2 State electricity board

7.12.3 State pollution control board

7.12.4 Factory inspectorate.

7.12.5 Food and drugs administration, Karnataka.

7.13 Equipments:

7.13.1 cGMP complied process equipments are provided to prevent cross contamination.

7.13.2 Automated material handling systems to minimize manual handling. 8.0 Design specification: (Room/Section wise):

Design specifications in minute details shall be finalized for each room/section of the Facility .Design Requirements with respect to following points shall be finalized & enclosed to this protocol

8.1 Room Dimensions (L x B x H).

8.2 Area in Sq. feet.

8.3 Floor.

8.4 Coving.

8.5 Walls.

8.6 Doors.

8.7 Door closure.

8.8 Vision panels.

8.9 Ceiling/ False ceiling.

8.10 Paint.

8.11 Electrical fittings, lighting fixtures.

8.12 Drainage.

8.13 Utilities Points.

8.14 Air inlet/ Return grills

8.15 Machine

8.16 Temperature

8.17 Humidity

8.18 Pressure differential

8.19 HVAC

8.20 Water system

8.21 Area Qualification ( AQ):

a) Pressure differential

b) Non- Viable particle count

c) Temperature mapping of raw material store

d) Temperature monitoring.

8.21.1 Microbial monitoring:

a) Settle plate count

b) Volumetric air sampling for viable count.

c) Swab test

d) Rinse analysis

e) Drainage swabs

9.0 Installation Qualification:

9.1 Purpose: Purpose of installation qualification is to establish documented evidence that the facility has been designed and constructed as intended and deviations, if any are justified & recorded.

9.2 Facility Layout (To Scale)

Approved layout of each floor (Ground floor, First floor and Service floor) shall be matched with the actual floor construction. Any deviation to the approved layout shall be documented, Justified and approved by corporate technical team & project head. Impact of the same shall be assessed with respect to product quality.

9.2 Facility within and outside shall be assessed with respect to compliance of cGMP’s related to location, surroundings and premises.

9.3 Room data sheets: Refer design requirements of each room/ area/section. Verify the compliance & record. Any deviation shall be documented, discussed & approved incase it is concluded that the deviation shall have no impact directly or indirectly on the product quality. If otherwise, required actions shall be taken & documented.

9.4 Termite treatment certificate, FDA license to manufacture drug products in the new facility, approved layouts (Floor wise), certificates from various contractors (civil, electrical) and from various government agencies shall be attached to installation qualification report.

9.5 Changes made in the facility layouts since the start of construction of the facility shall be documented, giving justification for each change made in the layout or design specifications.

9.6 Acceptance Criteria:

The facility shall meet approved design requirements and floor layouts. Any change in the approved design or layout shall be through change control and documented. Deviations if any shall be justified, assessed, approved and documented.

10.0 Operational qualification:

Every room/ section on each floor shall be checked for flawless and smooth functioning of the following as applicable. Any discrepancy shall be identified, corrected and documented.

10.1 Opening of the doors.

10.2 Closing of the doors.

10.3 Door locks (Lock & Unlock)

10.4 Door handles & hinges

10.5 Door closure.

10.6 Light source & fixtures.

10.7 Electric points & their earthling.

10.8 Water points.

10.9 Compressed air use points.

10.10 Air Handling Unit.

10.11 Differential pressure.

10.12 Drain Points.

10.13 Acceptance Criteria:

Intended out put of the above features shall be met for each room/section as applicable.

11.0 PERFORMANCE QUALIFICATION:

Performance Qualification of various support services provided in each room are detailed in the respective utility protocols

12.0 Requalification criteria:

12.1 Any change/ modification is made in the facility design or layout. The affected area shall be requalified and the room data sheet of the affected area shall be updated to incorporate the change(s) made.

12.2 Any change made in the existing area support services or new or additional features are added to the room.

13.0 Discussions & Summary:

Data collected during the execution of this protocol shall be compiled and evaluated and discussed. Summary report shall be prepared.

14.0 Conclusions and final approvals:

From the data compiled, a summary report shall be prepared. Corporate technical team shall review and approve the final summary report prior to handling of the building for regular use.

15.0 Attachments:

Approved drawings

Door specifications

Certificates