Name of the manufacturing unit

Address
Mfg Lic.no.
Validity of License.
Constitution of the firm
List of Directors/Partners/Proprietor
License issuing authority
Categories of drugs permitted to be manufactured
Specify whether COPP has been issued to the firm
Name and Designation of the Inspecting team members
Site Specific Data
No. of Products manufactured at site (during last year)
No. of manufacturing blocks
No. of Technical Personnel in Manufacturing
No. of Technical Personnel in QA
No. of Technical Personnel in QC
No. of Technical Personnel in Microbiology
No. of Technical Personnel from other Department
No. of Technical Personnel in R&D
No. Of technical personnel in Formulation development
No. of Samples drawn by QC (during last year)
No. of Samples declared OOS (during last year)
No. of samples declared NSQ by Govt. Analyst (during last year). Collect
reasons for such failures and annexe with this checklist

Observations should be descriptive without ambiguity and answer like "Yes" or "No" should be avoided
1 Building and premises: -

Observation
1.1 Sch-M, Specify whether the whole facility is separated,
dedicated and is not a part of any other non-drug
facility.
1.2 Sch-M, Specify whether the surroundings of manufacturing
area is clean and as per the SOP prescribed in this
regard. (Mention the SOP nos.)
1.3 Sch-M, Describe the pest, insects, birds and rodents control
system followed in the premises. Specify pest control
schedule- area wise, along with materials and
methods used.

1.4 Sch-M, What measures have been taken to make Interior

surface (of walls, floors, and ceilings) smooth and
free from cracks, and to permit easy cleaning Specify
material of construction and finish for
walls, ceiling, floor, coving etc. i.e. whether Epoxy
or PU coated, kota / granite stone with epoxy sealed
joints, solid / GI / gypsum / cal. Silicate board ceiling
with epoxy, PU or any other pre- fabricated panel
(GRP, powder coated SS or Aluminium etc.) paint.

1.5 Sch-M, Specify the lux level maintained in various parts of

the premise (Storage area, manufacturing area
specially visual inspection, Laboratory areas etc.).

1.6 Sch-M, Specify the air handling system used in various areas
i.e. stores, production, packing, QC areas.

1.7 Sch-M, Specify drainage system which prevents back flow

and entry of insects and rodents into the premises.
Specify number and location of drains installed.

2 Ancillary areas: -
2.1 Sch-M, Specify the position of rest and refreshment rooms
and mention whether they are separated and not
leading directly to the manufacturing and warehouse
areas.
2.2 Sch-M, Are there general change rooms in plant? specify
number of washing station & toilets provided for
number of users.
2.3 Sch-M, Specify whether primary clean garments are
provided for each personnel entering the factory
premises.
2.4 Sch-M, Is there in-house general laundry for garment
washing / cleaning? If not how garment washing is
carried out and monitored.
2.5 Sch-M, Para Whether change room facilities separated for both
sexes.
2.6 Sch-M, Para Whether maintenance workshop is separated and
away from production.
3 Security system:-
3.1 WHO TRS Is the men & material movement inside the factory
premises, observed & checked through security
system.

3.2 WHO TRS Is CCTV available to control the Entry & Exit from
Factory premises?

3.3 WHO TRS Is there a system for identifying persons visiting the
factory ? How?

3.4 WHO TRS What is the precautionary activity taken for the
movement of carriers i.e. vehicles?

4 Water & Compressed air system: -

4.1 Sch-M, Para Verify whether a current drawing of the water system
showing all equipment in the system from inlet to the
points of use is available.

4.1.1 Sch-M, Para Specify the MOC of the water storage tank (Both
PW & WFI) and its pipe line.

4.1.2 Sch-M, Para Specify weather storage tank for WFI is steam
jacketed.

4.2 Sch-M, Para Specify whether water system

validation/qualification has been carried out as per
protocol and reports have been prepared and
maintained.

4.3 WHO TRS- Whether IQ protocol include at least facility review,

970 equipment specification vs. design, welding
roughness testing on pipelines, absence of dead
points / section in the pipelines, pipe and tank
passivation, drawings, SOP for operations, cleaning,
sanitation, maintenance and calibration
of gadgets. Whether its report includes Conclusion
/ Summary, Data tables, Results, Conclusions,
Protocol reference, Revision and approval signatures.

4.4 WHO TRS- Whether OQ protocol includes at least System

production capacity (L/min), Flow type and water
rate, Valve operation, Alarm system operation and
Controls operation? Whether its report includes
Conclusion / Summary, operations performed Data
tables, Results, Conclusions, Protocol reference,
Revision and approval signatures.
4.4 Whether OQ protocol includes at least System
970 production capacity (L/min), Flow type and water
rate, Valve operation, Alarm system operation and
Controls operation? Whether its report includes
Conclusion / Summary, operations performed Data
tables, Results, Conclusions, Protocol reference,
Revision and approval signatures.

4.5 WHO TRS- Please specify whether Phase 1, Phase 2 and

970 Phase 3 studies carried as part of PQ stages?

4.6 WHO TRS- Phase 1: Whether the operations parameters, cleaning

970 and sanitation procedures & frequencies defined.
Whether daily sampling records for every pre-
treatment point and usage point for a period of

4.7 WHO TRS- PHASE 2: Whether daily sampling records for every
970 pre-treatment point and usage point for a period of 4
to 5 weeks after Phase 1 maintained and reviewed.

4.8 WHO TRS- PHASE 3: Whether weekly sampling records available of every usage point for a one-year period.
970

4.9 Sch-M Specify source of raw water and give details of treatment processes, sampling points, distribution and storage system for r

4.1 Sch-M Verify whether the softener column is regenerated as per

the specified SOP.

4.11 Sch-M Specify whether the quality of potable water used for the
preparation of purified water meets the requirement of
Schedule M in respect of microbiological limit.
4.12 Sch-M Specify whether the quality of Purified Water used for the
preparation of WFI meets the requirement of IP/BP/USP.

4.13 Sch-M What is the process for preparation of Water for

Injection (WFI)?

4.14 Sch-M Specify the process of sanitisation of SS storage tank of

WFI.
4.15 Sch-M Specify whether the quality of WFI meets the requirement
of IP/BP/USP & Schedule M.

4.16 Sch-M Specify whether WFI is used for:

1) Bulk preparations of liquid injections
2) Final rinse of product containers for sterile preparations.
3) Final rinse of machine parts (for sterile preparations)
4) Preparation of disinfectant solutions for use in critical
areas (for sterile preparations.)

4.17 Sch-M How bio burden in purified water & WFI are controlled / reduced (Mention the SOP no. followed in this regard).

4.17.1 Sch-M Specify whether WFI has been stored and circulated above 70 degree centigrade.

4.18 WHO TRS- Verify whether the circulation rate of purified water
970 & WFI is at least twice the storage capacity of the holding
vessels per hour.

4.19 WHO TRS- Verify the Dead leg of non returned valve at the discharge point.
970
4.2 WHO TRS- Specify how the circulation loop is sanitised. Verify the SOP.
970
4.21 WHO TRS- Specify whether spray ball is used to wet the surface of head space in the storage vessel.
970
4.22 WHO TRS- Specify whether pressure release valves are provided in the storage vessel.
970
4.23 Sch-M How water tanks are cleaned periodically and records maintained thereof.

4.24 WHO TRS- Specify whether on line TOC test is available for
970 WFI & PW.

4.25 PIC/S Examine the record of the daily check of balances in the
dispensing area.
4.25 Examine the record of the daily check of balances in the
Guidelines dispensing area.

4.26 Sch-M Specify the arrangement for preparation of pure steam &
its use.

4.27 Sch-M Specify whether pure steam (condensate) used in

production meets the microbiological specification of not
more than 10 cfu/100ml and IP/BP/USP specifications of
WFI.

4.28 WHO TRS- Verify PQ of the PSG.

970
4.29 Sch-M Specify the system in place for the compressed gases / air
used in the facility.
4.3 ISO/PICS Verify the qualification documents of compressed air system specially where it comes in contact with product or primary

4.31 WHO TRS- Specify whether action and alert limits are followed based
970 on qualification of water and compressed
Air system.

5 Disposal of waste(Ambient protection):-

5.1 Sch-M Specify the system of disposal of sewage, and effluents
(solid, liquid, and gas) from the manufacturing site.
(Enclosed the copy of NOC obtained from State Pollution
control board in this regard.)

5.2 Sch-M Mention the procedure for storage and disposal of rejected drugs and applicable SOP.

5.3 Sch-M Whether adequate records are maintained for the disposal of waste.

5.4 Sch-M Whether provision for disposal of bio-medical waste made

as per the provisions of the Bio Medical Waste
(Management and Handling) Rules
1996.

6 Health, clothing and sanitation of workers: -

6.1 Sch-M Whether all personnel prior to employment have
undergone medical examination including eye examination
and are all free from Tuberculosis, skin and other
communicable or contagious diseases & thereafter at
regular intervals.

6.2 Sch-M Whether investigational reports, e.g. of X rays etc.

preserved.
Whether records of such medical examination are
maintained thereof

6.3 Sch-M Specify whether employees report their illness to the supervising authority before entering into the production area.
6.4 Sch-M Specify whether person from infectious disease is barred to enter into production area.

6.5 Sch-M Specify if any unhygienic practise is observed within the manufacturing areas.

6.6 Sch-M Whether all personnel are trained to ensure high level of
personal hygiene. Mention the SOP no. followed in this
regard.

6.7 Sch-M Specify whether cross over bench is in place in the change
room and if so whether it rules out the possibility of dust
particle entering the clean side.

6.8 Sch-M Whether arrangements provided for cleaning of outside

dust and dirt from foot.
7 Training:-
7.1 Sch-M Specify whether basic training on GMP is provided to all
personnel attached to production and quality control
activity at the time of induction.

7.2 Sch-M Specify whether specific training related to the job duty are
provided to all personnel at the time of induction.

7.3 WHO TRS- Specify whether continuous training is provided.

986
7.4 WHO TRS- Specify whether concept of QA and its importance is part of training session.
986
7.5 WHO TRS- Are all the persons associated with various production
986 activities properly trained as per guidelines provided in
WHO working document. Verify the assessment records of
the training of few selected people who are associated with
critical operations and procedure

8 Warehousing Area:-
8.1 WHO TRS- Is access to the area restricted to authorised personnel only.
986

8.2 Sch-M Whether adequate areas have been allocated for

warehousing of Raw Materials, intermediates, Packaging
Material, products in quarantine, finish products, rejected
or returned products. How are these areas marked or
segregated.
Please specify the total area provided for warehousing.
8.3 Sch-M How the warehousing areas being maintained to have good
storage conditions. Are they clean and dry and maintained
within specified temperature limits?

8.4 WHO TRS- Is there any SOP defining maximum exposure time at
986 room temperature for thermo labile materials i.e. prior to
storage in a refrigerator.

8.5 Sch-M Specify the storage arrangement provided for materials

which are sensitive to temperature, humidity and light and
how the parameters are monitored.
Is cold room or deep freezers required for storage of
goods?

8.6 WHO TRS- Verify the Thermal mapping of the cold rooms or deep freezers
986

8.7 Sch-M Whether receiving and dispatch bays are maintained to protect in coming and out going materials.

8.8 Sch-M How incoming materials are treated and cleaned before
entry into the plant.
Please specify the cleaning system for the outer surface of
the container.

8.9 Sch-M How quarantined materials are segregated from other

materials.
How access to quarantined area is restricted.

8.1 Sch-M Specify the system followed for storing passed raw materials.

8.11 Sch-M Whether proper racks, bins and platforms have been provided for the storage.

8.12 WHO TRS- What is the control on entry of material and men into the sampling area? Whether reverse LAF have been provided for sa
986

8.13 Sch-M Specify the storage arrangement provided for primary packaging materials.

8.14 Sch-M Specify the arrangements provided to sample the primary packaging materials foils, bottles, etc. which are used as such.

8.15 WHO TRS- Specify sampling plan used.

8.15 Specify sampling plan used.
986

8.16 WHO TRS- Which type of sampling tools are used and how they are cleaned, dried and maintained.
986
8.17 WHO TRS- How containers are cleaned before and after sampling. (Specify whether the sampling is carried out as per the current SOP
986

8.18 Sch-M What provisions have been made for segregated storage of rejected, recalled or returned materials or products. How is the

8.19 Sch-M How printed secondary packaging materials are stored in safe, separate and in secure manner.

8.2 Sch-M How printed packaging materials, product leaflets etc. are stored separately to avoid chances of mix- up?

8.21 Sch-M How labels, cartons, boxes, circulars, inserts and leaflets are controlled. ?

8.22 Sch-M How records of receipt of all labelling and packaging materials are maintained.

8.23 Sch-M Whether unused packaging materials return to the store or destroyed.

8.24 Sch-M How returned/unused packaging material like foils is controlled so as to prevent contamination and cross- contamination.

8.25 Sch-M Specify the arrangement provided for dispensing of starting materials.

8.26 WHO TRS- What is the control on entry of material and men into the dispensing area? Whether reverse LAF have been provided for d
986

8.27 WHO TRS- Whether pressure differential is maintained between the dispensing and adjacent areas.
986
8.28 WHO TRS- Specify the pressure differential maintained.
986
8.29 Sch-M Examine the record of the daily check of balances in the dispensing area.

8.3 WHO TRS- How containers are cleaned before and after dispensing. Who carries out the dispensing?
986
8.31 WHO TRS- Specify whether appropriate air velocity is maintained in sampling & dispensing areas which rule out any influence in the
986

8.32 Sch-M Specify whether the dispensing is carried out as per the current SOP.

8.33 Sch-M Specify whether dispensed material for each batch of final product are kept together and conspicuously labelled.
8.34 Sch-M What steps are taken against spillage, breakage and leakage of containers?

8.35 Sch-M How highly hazardous, poisonous and explosive materials, narcotics, and psychotropic drugs are handled and stored. How

9 Raw Materials: -
9.1 Sch-M Please specify the procedures followed for receiving and processing of in-coming materials (Starting materials and packin

9.2 Sch-M Whether first in / first out or first expiry principal has been adopted.

9.3 Sch-M How they are labelled and stored as per their

9.4 Sch-M Whether incoming materials are purchased from approved vendors.

9.5 Sch-M Whether list of approved vendors is available to the user.

9.6 WHO TRS- Specify the norms of vendor qualification.

986
9.7 Sch-M How damaged containers are identified recorded and segregated

9.8 Sch-M Whether each batch of a consignment is considered for sampling, testing and release.

9.9 WHO TRS- Whether all the containers of each batch of starting materials sampled for identification test.
986

9.1 Sch-M Whether labels of raw material in the storage area have information like ;

(a) designated name of the product and the internal code

reference, where applicable, and analytical reference
number;

number;

(c) the status of the contents (e.g. quarantine, under

test,released,approved, rejected); and
(d) The manufacturing date, expiry date and re-test date.

9.11 Sch-M Whether separate areas are provided for under test, approved and rejected materials.

9.12 Sch-M How the containers from which samples have been drawn labelled.

9.13 Sch-M Please specify the procedures by which it is ensured that the raw materials which has been released by the Quality Control

10 Production Area for Non Sterile preparation:-

10.1 WHO TRS- Verify whether access to production area is restricted to authorised personnel only.
986
10.2 WHO TRS- Whether the facility is provided with a well-sealed structure with no air leakage through ceilings, cracks or service penetra
986

10.3 WHO TRS- Whether entry and exit doors, for materials and personnel, have an interlock mechanism or other appropriate system to pre
986

10.4 WHO TRS- Specify the procedures for entry of maintenance people into the production area.
986
10.5 WHO TRS- Whether the change rooms have an arrangement with step-over/cross-over bench.
986
10.6 Sch-M Is there any cris cross flow of materials and men?

10.7 Sch-M Whether the premises and equipment are appropriately designed and installed to facilitate cleaning and decontamination.

10.8 WHO TRS- Specify the position of IPQC lab in the manufacturing area.
986
10.9 Sch-M Specify whether non storage areas are used for storage of any material.

10.1 WHO TRS- Specify the provisions for storage of dirty, washed and cleaned equipment in process areas.
986

10.11 Sch-M Specify how service lines are identified for nature of supply and direction of the flow.

10.12 WHO TRS- Whether service lines in production areas are through service pendants. If not, how they are placed so as to avoid accumul
986

11 Air Handling Systems (HVAC):-

11.1 WHO TRS- Pl qu
ease specify whether following parameters are alified:
986 (IQ,OQ,PQ)

ppropriate

11.2 WHO TRS- Verify the SOPs for AHUs operation and cleaning.
986
11.3 WHO TRS- Specify whether the facilities and premises have following
986 basic air-handling characteristics:
a) The absence of direct venting of air to the outside.
b) Whether the facility is maintained at a negative air
pressure to the environment.
c) The precaution taken to prevent the infiltration into the
core areas.
d) Whether appropriate air pressure alarm systems as well
as alert and action limit is provided.
e) The type of HEPA filters used in the HVAC
system
f) Whether the change rooms are supplied with same
quality of air as supplied to the working area. g) The
measures taken to prevent air flow from the primary
packing area to the secondary packing area.

11.4 WHO TRS- Whether HVAC system description includes:

986 1) Schematic drawings detailing the filters and their
specifications
2) Number of air changes per hour
3) pressure gradients

11.5 WHO TRS- Specify the emergency power systems in case of power failure.
986
11.6 WHO TRS- Specify whether recirculated air is used. If yes, specify the proportion of fresh air supplied.
986

11.7 WHO TRS- Whether risk assessment study has been carried out in case of return air/ recirculated air system. Verify the records thereo
986

11.8 WHO TRS- Specify what precaution has been taken during filter change of AHUs.
986
11.9 WHO TRS- Whether all exhaust systems from the facility, including dust extraction systems, vacuum system exhaust, fluid bed drier e
986
11.1 WHO TRS- Whether all exhaust points outside the building are located
986 as far as possible from air entry points, exit points and at a
high level, to minimize the
possibility of re-entrainment of exhaust air.

11.11 WHO TRS- Whether the return air ducts are checked periodically for dust accumulation.
986
11.11 Sch-M Whether the dust collectors are located in a room maintained at a negative pressure.

11.12 WHO TRS- Whether the filters cleaning facility is maintained at negative pressure.
986
11.13 WHO TRS- Whether records for safe disposal of all contaminated filters and dust are maintained.
986
11.15 WHO TRS- Specify whether total No. of AHUs used to cover the whole production Area is commensurate with the requirements
986

11.16 WHO TRS- Specify the Terminal Air Filter of various core areas.
986
11.17 WHO TRS- Specify the no. of Air Change maintained in various core areas.
986
11.18 WHO TRS- Specify the pressure balancing to segregate different areas.
986
11.19 WHO TRS- Are the returns risers cleaned during Product
986 Change Over?
11.2 WHO TRS- Verify if the AHU's / HVAC systems have been shut down. If yes the reasons there of such as cleaning & maintenance &
986

12 Cleaning Validation:-
12.1 Sch-M Is a validation performed to confirm cleaning effectiveness?

12.2 WHO TRS- Does the protocol define the selection criteria for products or groups of products subject to cleaning validation?
986

12.3 WHO TRS- Is data produced supporting the conclusion that residues were removed to an acceptable level?
986

12.4 WHO TRS- Specify whether the validation is implemented to verify

986 cleaning of:
1 )Surfaces in contact with the product
2) After a change in product
3) Between shift batches.

12.5 WHO TRS- Specify whether the Validation Strategy include contamination risks & equipment storage time.
986

12.6 WHO TRS- Whether Quality Control responsible of the sampling for cleaning verification?
986

12.7 WHO TRS- Whether personnel engaged in cleaning, sampling etc. trained.
986
12.8 WHO TRS- Specify whether acceptance limits been set for cleaning
986 verification and are based on following criteria:
1) Visually clean.
2) 10 ppm in another product.
3) 0.1% of the therapeutic dose?

12.9 WHO TRS- Specify whether detergent residues and degradation products are investigated during validation.
986

12.1 WHO TRS- Whether validation records include : Recovery study data,
986 Analytical method, Acceptance Criteria, Swab recovery
test,
Signatures of the Quality Assurance Manager, Signature of
the employee in charge of cleaning verification from
Production and Quality Control.

13 Manufacturing Operations and Controls:-

13.1 Sch-M Whether the contents of all vessels and containers used in manufacture and storage is conspicuously labelled with the nam

13.2 Sch-M Whether the products not prepared under aseptic conditions are free from pathogens like Salmonella, Escherichia coli, Pyo

13.3 Sch-M If yes, pls give brief account of measures taken to assure freedom from pathogens.

13.4 WHO TRS- Verify whether handling of materials and products are carried out in accordance with the relevant
986

13.5 WHO TRS- Specify Whether any deviation is approved in writing by a designated person and recorded.
986
13.6 WHO TRS- Is there an approved SOP for In process check?
986
13.7 WHO TRS- Is the personnel clothing clean, unstained & dust free, including shoes?
986
13.8 WHO TRS- Is there a cleaning SOP for slippers or shoes that is being used in the manufacturing area?
986
13.9 WHO TRS- Whether process hold time studies has been carried out for various stages of production
986
14 Precautions against mix-up and cross-contaminations:-
14.1 Sch-M Whether proper AHU, pressure differential, segregation, status labelling have been provided to prevent mix-up and cross-

14.2 Sch-M Pls specify the areas of dust generation and mechanism involved in controlling the dust

14.3 Sch-M Do all the areas have their own independent air locks separately for men and material entry.

14.4 Sch-M What criteria of pressure differential has been set for production v/s adjoining areas.

14.5 Sch-M Whether processing of sensitive drugs like Beta lactam Antibiotics and Sex Hormones is done in segregated areas with ind

14.6 Sch-M Please specify what measures has been taken to prevent contamination of products with Beta Lactam Antibiotics, Sex hor

14.7 Sch-M What measures has been taken to prevent mix- ups during various stages of production.

14.8 Sch-M Whether equipments use for production are labelled with their current status.

14.9 Sch-M Whether packaging lines are independent and adequately segregated.

14.1 Sch-M How line clearance is performed. Whether records of line clearance is maintained according to appropriate checklist.

14.11 Sch-M Whether separate carton coding area has been provided or online carton coding is performed How carton coding procedur

14.12 Sch-M Please specify how temperature, humidity and air filtration are controlled in the areas where raw material and/or products

14.13 Sch-M How access of authorized persons to manufacturing areas including packaging is controlled.

14.14 Sch-M Whether separate gowning provision is followed before entering the core areas.

14.15 Sch-M Whether segregated secured areas for recall or rejected materials or for such material which are to be processed or recover
14.16 Sch-M Whether various operations are carried out in segregated areas.

14.17 Sch-M Are doors of all core areas closed at all times with interlock arrangements?

14.18 Sch-M Specify whether any SOP is followed to verify the effectiveness for prevention of cross contamination.

14.19 WHO TRS- Specify whether critical operations are carried out in closed system.
986
14.2 WHO TRS- Specify the methods followed for product change- over.
986
15 Sanitation in the Manufacturing areas:-
15.1 Sch-M Specify the cleaning procedure of the manufacturing areas and verify with the SOP in this regard.

15.2 Sch-M Whether cleaning procedure is validated.

15.3 Sch-M Whether a routine sanitation program is in place.

15.4 Sch-M Verify the SOP & the records in this regard.

15.5 Sch-M Does the location facilitate cleaning of equipment as well as the cleaning of the areas in which they are installed?

15.6 Sch-M Whether production area is adequately lit.

15.7 Sch-M Mention lux levels observed in production, visual inspection and other areas.

15.8 Sch-M Specify in detail the procedure followed during product changeover.

16 Equipment: -
16.1 Sch-M Whether the equipment are designed aiming to minimize risk of error and permit effective cleaning and maintenance in or

16.2 Sch-M Whether all equipment are provided with log book.

16.3 Sch-M Please specify the procedures to clean the equipment after each batch production.

16.4 Sch-M Whether validity period for use after the cleaning of equipment is specified.

16.5 Sch-M Whether separate area is provided for storage of machine parts etc.

16.6 Sch-M Whether balances and other measuring equipments with appropriate range are available in the Raw Material stores & prod

16.7 Sch-M Specify material of construction of contact parts of the production equipments.

16.8 Sch-M Which types of lubricants are used in the equipment. Specify the quality and control reference No. of these lubricants

16.9 Sch-M Specify the procedures to remove defective equipments from production areas.
16.1 WHO TRS- Verify whether washing and cleaning of equipment are not a source of contamination.
986

16.11 Sch-M Whether all equipment is provided with an ID NO.

16.12 WHO TRS- Specify the procedures to clean the equipment after each batch production and verify with the SOP.
986

16.13 WHO TRS- Specify whether CIP or SIP is in place.

986

16.14 WHO TRS- Specify whether the CIP / SIP system is qualified
986
16.15 WHO TRS- Are there cleaning agent labelled with a catalogue no.
986 indicating that they were received through the warehouse.

16.16 WHO TRS- Are there records for preparation of cleaning agent?
986
17 Produ ction Area fo
r Sterile Preparation
17.1 Building and Facilities:-
17.2 Sch-M Sch-M Specify the building is devoid of cracks especially in the Critical solutions preparation rooms, Filling rooms, Sealing room

17.3 Are the location of services like water, steam, gases etc. Such that the servicing or repairs can be carried out without any t

17.4 Sch-M Specify water lines pose any threat of leakage to the critical area

17.5 Sch-M Specify the manufacturing areas clearly separated into

following Support Areas:
1) Washing of containers & closures
2) Storage of washed containers & closures
3) Sterilization of containers & closures
4) Preparation of bulk solution ( critical/non critical)
5) Change room

17.6 Sch-M Specify de-cartoning areas to remove outer cardboard wrappings of primary packaging materials segregated from the wash

17.7 Sch-M Specify whether particle shedding materials like wooden pallets, fibre board drums, cardboards etc. are taken into the prep
17.8 Sch-M Specify in the classified areas:
1) Walls are flat, smooth and devoid of recesses.
2) Surface joints like electric sockets, gas points flushed
with walls.
3) Joints in the ceiling are properly sealed
4) Air grills and lights flushed with the ceiling.
5) Grade A & B areas devoid of sinks and drains.
6) Doors and windows made up of non shedding materials.
7) Doors open towards higher pressure areas and close
automatically due to air pressure.

17.16 WHO TRS- Is there a glass panel between critical area & support area so that all operations in Grade A & B areas can be supervised fr
961
ANNEXE-06

17.17 WHO TRS- Fire extinguishers are suitably fastened to the walls without gaps.
961
ANNEXE-06

17.18 Sch-M Quality of the furniture used is smooth & washable and made of SS316.

17.19 Sch-M Change rooms entrance provided with air locks before entry to the sterile product manufacturing areas.

17.2 Sch-M How many change rooms are provided to enter into the critical areas?

17.21 WHO TRS- Specify an appropriate inter- locking system with visual and/or audible warning system installed to prevent the opening of
961
ANNEXE-06

17.22 Sch-M Are the critical and support areas provided with intercom telephones or speak phones for communication purposes.

17.23 Sch-M Specify the critical areas and support areas provided with suitable air- locks or pass boxes with proper interlocking arrang

17.24 WHO TRS- Specify whether dynamic pass box is used for material transfer between two different air class.
961
ANNEXE-06

17.25 Sch-M Specify the method of transfer of sterile rubber bungs & aluminium caps to the aseptic area.
17.26 Sch-M Specify whether grade A/B area is devoid of sinks and drains.

18 Air Handling System (Central Air Conditioning):-

18.1 Sch-M Specify whether the Air Handling Units for sterile product manufacturing area are separated from those for other areas

18.2 Sch-M Give the Background Grade of air for following critical
areas:
1) Aseptic filling area
2) Sterilized components unloading area for aseptic filling.
3) Batch manufacturing area for aseptic filling
preparations.
4) Component washing and preparation area.
5) Change rooms to enter into Critical area.

18.3 WHO TRS- Specify the steps taken in air handling system to achieve the Grade A, B, C and D of air as per designated classified areas.
961
ANNEXE-06

18.4 Sch-M Specify the recovery time of B & C zone from the time of personnel leaving the room after completion of operations and

18.5 Sch-M Specify whether filling operations are challenged initially and there after periodically by simulation trials including sterile

18.6 WHO TRS- Specify the procedure followed for medial fill and the acceptance criteria.
961
ANNEXE-06

18.7 WHO TRS- Whether the medial fill trial is based on worst case situation taking into consideration all interventions, activities occurring
961
ANNEXE-06

18.8 WHO TRS- Whether simulation tests are repeated at defined intervals and after any significant modification to HVAC system, equipm
961
ANNEXE-06

18.9 Sch-M Specify the number of air changes in Grade A/B

and Grade C areas.

18.1 Sch-M Specify the air velocity maintained in Grade A Laminar Air Flow stations

18.11 Sch-M Specify the differential pressure between areas of different environmental standards.

18.12 Sch-M Specify type of manometer installed for measurement and verification of Air Pressure Differential.

18.13 WHO TRS- Specify the air classification in final change room to enter A/B area.
961
ANNEXE-06

19 Environmental Monitoring:-
19.1 Sch-M Specify the temperature and humidity maintained in the critical areas.

19.2 WHO TRS- Verify the area qualification records and specify whether
961 the following were taken into consideration :
1) No. of Persons
ANNEXE-06 2) ACPH (Air Changes per hours)
3) Particle count (Static & Dynamic)
4) Viable count (Static & Dynamic)
5) Temperature & Humidity
6) Air Sampling location and interpretation of results
(Both viable and non-viable)
7) Whether the above method is in compliance with ISO
14644-1
8) Action and Alert limits for all the above parameters

19.3 Sch-M Mention the periodic monitoring frequencies of the

followings:
1) Particulate counts
2) HEPA filters integrity testing
3) Air Change rates
4) Air pressure differentials
5) Temperature and Humidity
6) Microbiological monitoring by settle plates and/
or swabs in Critical areas & Other areas

19.4 Sch-M Does a written Environmental Monitoring Program exist?

19.5 Sch-M How long the settle plates are exposed in Grade A
and other areas.
19.6 Sch-M Verify the records of microbiological results also specify whether alert and actions limits are followed or not.

19.7 Sch-M What action is taken in case particulate and microbiological monitoring counts exceed the limits?

19.8 WHO TRS- Specify what parameters are reassessed and approved before starting production and in case of major engineering modific
961
ANNEXE-06

20 Garments:

20.1 Sch-M Specify type of garments used in critical areas?

20.2 Sch-M Specify type of Zips used in garments

20.3 Sch-M Whether garments used in critical areas are sterile.

20.4 Sch-M Specify the process of sterilization of the garments

& the practise followed to carry the sterilised garments to
the final change room.

20.5 Sch-M Are garments,masks,gloves are changed at every work session?

20.6 Sch-M Are the gloves used made of latex or other suitable plastic material

20.7 Sch-M Are powder free gloves used in clean rooms

20.8 Sch-M Are the gloves long enough to cover the wrists completely and allow the over-all cuff to be tucked in

20.9 Sch-M Are the foot-wear used made of plastic or rubber material

20.1 Sch-M Are the foot-wear daily cleaned with a bactericide

20.11 Sch-M Does the safety goggles / numbered glasses worn inside the critical areas have side extensions
20.12 Sch-M Are safety goggles sanitized by a suitable method

20.13 Sch-M Specify the garment changing procedure documented

20.14 Sch-M Specify whether operators are trained in garment changing procedure.

20.15 Sch-M Specify a full size mirror been provided in the final change room to ascertain that the operator has appropriately attired in

20.16 WHO TRS- Specify how the garments used in clean areas are cleaned and sterilized.
961
ANNEXE-06

21 Sanitation:

21.1 Sch-M Specify the SOP followed for sanitation of sterile processing facilities and mention the SOP nos.

21.2 Sch-M Specify whether employees carrying out the sanitation of critical areas are specially trained for this purpose.

21.3 Sch-M Verify the training records.

21.4 Sch-M Specify the sanitizing agent/s used.

21.5 Sch-M Specify the quality of water used for preparation of sanitising solution.

21.6 Sch-M Specify the disinfectant used for hand sprays?

21.7 Sch-M Specify whether disinfectant solutions are filtered through membrane into suitable sterile containers or sterilized before us

21.8 Sch-M establishment of their germicidal properties &

verify the records

21.9 Sch-M Specify whether fumigation is carried out in critical areas. If yes, specify fumigating agent and its conc. used.

21.1 Sch-M Specify whether any SOP exist for the purpose of fumigation if so mentioned the SOP nos.

21.11 Sch-M Specify the cleaning procedure of critical areas.

21.12 WHO TRS- Specify whether particle monitoring in Grade A zones is undertaken for the full duration of critical processing including e
961
ANNEXE-06

21.13 WHO TRS- Specify whether particle monitoring in Grade B zones is undertaken for the full duration of critical processing.
961
ANNEXE-06

21.14 Sch-M Whether more than one sanitizing agent is used in rotation. If yes list the sanitizing agents their concentration and frequen

22 Equipment:
22.1 Sch-M Specify whether the unit- sterilizers are double ended with suitable inter-locking between the doors.

22.2 Sch-M Specify the initial effectiveness of sterilization process established by using microbial spore indicators.

22.3 Sch-M Specify whether thermal Mapping of heat sterilizers is carried out on regular basis. Check records.

22.4 Sch-M Specify suitable vent filters and recording thermographs provided in autoclaves & dry sterilizers.
22.5 Sch-M Specify HEPA filters for cooling air and recording thermographs provided in DHS/Tunnel.

22.6 WHO TRS- Specify whether provisions of CIP or SIP are available.
961
ANNEXE-06

22.7 Sch-M Specify whether pure steams are in use.

22.8 Sch-M Specify filter integrity test carried out before and after the filtration process.

22.9 Sch-M Specify the material of construction of the equipment & glass containers.

22.1 Sch-M Specify the tubing used in critical areas

22.11 Sch-M Specify the qualifications of critical equipment.

22.12 WHO TRS- Verify the qualification, protocol and reports for the critical equipment.
961
ANNEXE-06
22.13 Sch-M Specify SOPs available for each equipment for its operation and cleaning.

22.14 Sch-M Specify whether the measuring devices attached to equipment calibrated at suitable intervals.

22.15 Sch-M Specify whether a written calibration program is available

22.16 Sch-M Specify whether calibration status documented and displayed on the equipment and the gauges

23 Manufacturing Process

23.1 Sch-M Specify whether the bulk raw materials and bulk solutions monitored for bio-burden periodically (solutions not to contain

23.2 Sch-M Specify the minimum possible time between the preparation of the solution and its sterilization or filtration through micro

23.3 Sch-M Specify the porosity of the filters when any external gases are coming into contact with the sterile product.

23.4 Sch-M Specify whether gas cylinders are kept out side of the critical areas.

23.5 Sch-M Specify the procedure of sterilization of washed containers.

23.6 Sch-M Specify whether the sterilized containers not used within an established time, rinsed with WFI and re- sterilized.

23.7 Sch-M Is each lot of the finished product filled in one continuation operation?

23.8 Sch-M Specify whether all critical process is validated. Verify the records.

23.9 WHO TRS- Verify the process validation protocol and reports for the critical operation.
961
ANNEXE-06

23.1 WHO TRS- Specify whether critical operations are carried out in closed system.
961
ANNEXE-06
24. Aseptic processing and sterilization by filtration:
24.1 Sch-M Specify whether the filling area is of Grade A
environment with Grade B background.

24.2 Sch-M Specify the room classification of solutions preparation area which is sterilized by filtration.
24.3 Sch-M Specify the filter used for sterilization of solution by filtration.

24.4 WHO TRS- Specify the maximum possible time used for filtration process.
961
ANNEXE-06

24.5 Sch-M Specify whether integrity of the sterilizing filters is verified before and after use. If so, by which method.

24.6 WHO TRS- Specify whether the personal working in the aseptic area are qualified for clean room procedure or not. If so verify the trai
961
ANNEXE-06

25 Product Containers & Closures:-

25.1 Sch-M Specify whether the containers and closures used comply with pharmacopoeia or other specific requirements.

25.2 Sch-M Specify whether Specifications, Test methods, Cleaning procedures, Sterilizing procedures etc. are available of the contain

25.3 Sch-M Specify whether the container & closures are compatible with the product without affecting its quality and purity. Verify t
25.4 Sch-M Specify whether containers and the closures are finally washed with WFI before sterilization.

25.5 Sch-M Specify whether a written procedure exist for washing of glass ampoules/vials.

25.6 Sch-M Specify whether the material quality of the stoppers and closures ensures that it does not affect the quality of the product a

26 Sterilization
26.1 Sch-M Whether the sterilizing processes have been validated (Dry heat, Moist heat, filtration, ETO, ionizations whichever applica

26.2 Sch-M Whether the validity of the process verified at regular intervals (at least annually)

26.3 Sch-M sufficient to sterilize one batch completely at one time. If

not specify controls and measures taken in lot
sterilizations.

26.4 Sch-M Whether biological indicators used in monitoring of sterilization.

26.5 WHO TRS- Verify that the probe is placed at the coolest point on the basis of validation studies
961
ANNEXE-06

26.6 WHO TRS- Verify the qualification, protocol and reports for the sterilisers
961
ANNEXE-06
26.7 Sch-M Whether the biological indicators stored and used as per manufacturers instructions. Whether quality

26.8 Sch-M

26.9 Sch-M Whether the label on the basket / tray or other carrier of
product / component clearly states:

Indicator (in case it has passed through sterilization

process)

26.1 Sch-M Whether sterilization records including thermographs and sterilization monitoring slips attached with the Batch Production

27 Sterilization (By Dry Heat)

27.1 Sch-M Whether the sterilization cycle recording device of suitable size and precision provided in DHS./ Tunnel

27.2 Sch-M Whether the position of temperature probes used for controlling and / or recording determined during validation and (whe

27.3 Sch-M Whether the chart forms a part of the batch record.
27.4 Sch-M Whether sterilization cycle validated only by biological indicator and chemical indicators or physical validation is also car

27.5 Sch-M Whether the time allowed reaching the required temperature before commencing the measurement of sterilizing time, sepa

27.6 Sch-M Are adequate precautions taken to protect the load during cooling after it has gone through the high temperature phase of a

27.7 Sch-M In case the cooling is affected with any fluid or gas in contact with the product , is it sterilized.

27.8 Sch-M Whether the equipment air inlet and outlets been provided with bacteria retaining filters

27.9 Sch-M In the process of sterilization by dry heat, does the

equipment have:
1 Air circulation facility within the chambers
2 Positive pressure to prevent entry of non-sterile air

27.1 WHO TRS- Verify the sterilizer loading pattern & whether is complied with the validated loading pattern.
961
ANNEXE-06

27.11 Sch-M Whether the process of dry heat sterilization intended to

remove the pyrogens
If so, has the validation been done with challenge tests
using endo-toxins

28.Sterilization (By Moist Heat)

28.1 Sch-M Whether recording of both temperature and pressure carried out to monitor the process
28.2 Sch-M Whether the control instrumentation independent of the monitoring instrumentation and recording charts.

28.3 Sch-M Whether the equipment has automated control and

monitoring system, if so, have these been
validated to ensure that critical process requirements are
met.

28.4 Sch-M Whether the system and cycle faults are recorded inbuilt and also observed by the operator and record maintained.

28.5 Sch-M Whether the readings of the thermograph during sterilization cycling are routinely checked by the operator against the read

28.6 Sch-M Whether the sterilizer fitted with a drain at the bottom of the chamber If so, does the record of temperature at this position

28.7 Sch-M Are frequent leak tests conducted on the chamber of the autoclave on each day of operation.

28.8 Sch-M Whether all items to be sterilized (other than sealed containers) are wrapped for sterilization.

28.9 Sch-M Whether the wrapping material allows removal of air and penetration of steam ensuring contact with the sterilizing agent a
28.1 Sch-M Whether the wrapping prevent contamination after sterilization

28.11 Sch-M Whether the steam used for sterilization is of

level which could cause contamination of the product or

equipment

29. Others
29.1 Sch-M Specify whether products released only after complete filling and testing.

29.2 Sch-M Specify whether result of the tests relating to sterility, bacterial endo-toxins are maintained in the analytical records

29.3 WHO TRS- Whether process hold time studies has been carried out for various stages of production
961
ANNEXE-06

30. Documentation and Records

30.1 Sch-M Whether all daily documents are filled correctly and timely.

30.2 Sch-M How the documents are designed, prepared, reviewed and controlled to provide an audit trail.

30.3 Sch-M Whether documents are approved signed and dated by appropriate and authorized person.

30.4 Sch-M Whether documents specify title, nature and purpose.

30.5 Sch-M Whether documents are regularly reviewed and kept up to date.

30.6 Sch-M Whether the records are made at the time of each operation in such a way that all significant activities concerning to the pr

30.7 Sch-M Whether data is recorded by electronic data processing system or by other means. If by electronic data processing system
30.8 Sch-M Whether master formula and detailed operating procedures for each product are available?

30.9 Sch-M Specify the duration of retaining the documents after the expiry of the respective product and who is responsible for its ma

Do the manufacturing records pertaining to manufacture of Sterile & Non-

Sterile products indicate the following details: Serial number of Batch
Manufacturing ,Record ,Name of the product, Reference to Master Formula
Record, Batch/ Lot number, Batch/ Lot size, Date of commencement and
completion of manufacture, Date of manufacture and assigned date of
expiry, Date of each step in manufacturing, Names of all ingredients with
reference number given by the quality control department ,Quantity of all
ingredients, Time and duration of blending, mixing etc. where ever
applicable, PH of solutions whenever applicable, Filter integrity testing
records, Temperature and humidity records whenever applicable, Records
of plate-counts whenever applicable, Results of
bacterial endo-toxin and toxicity, Records of weight or volume of drug
filled in containers, Bio burden records before sterilisation, Leak test
records, Inspection records, Sterilization records including load details,
date, duration, temperature, pressure etc. Container washing & testing
records, Total number of containers filled, Total number of containers
rejected at each stage, Theoretical yield, permissible yield, actual yield and
variation there of, Clarification for variation in yield ,beyond permissible
yield, Reference number of relevant analytical reports, Details of re-
processing, if any, Names of all operators carrying out
different activities, Environmental monitoring records,

31 Labels and Other Printed Materials:-

31.1 Sch-M Whether the printing is in bright colour and legible on labels and other printed materials?

31.2 Sch-M How printed labels (art work) are approved. Verify the SOP.

31.3 WHO TRS- Specify whether cut labels or rolled labels are used.
986
31.4 Sch-M Whether the labels comply with requirements of
Rule 96 & 97 & other relevant provisions

32 Master Formula Records: -

32.1 Sch-M How master formula records for each product are prepared, authorized and controlled.
32.2 Sch-M Whether master formula is batch size specific.

32.3 Sch-M Whether master formula record covers all the

32.4 WHO TRS- Whether master formula record covered all the points as prescribed in WHO-TRS 986 & PIC/S guidelines
986

33 Batch Processing / Manufacturing Records:-

33.1 Sch-M Whether the BPR/BMR for each product is prepared on the basis of currently approved master formula.

33.2 Sch-M Whether BPR / BMR covered all the points as

33.3 WHO TRS- Whether BPR / BMR covered all the points as prescribed in WHO-TRS 986 & PIC/S
986

33.4 Sch-M Whether all the documents generated during

Batch production are attached with the BPR /BMR

34 Batch Packaging Records: -

34.1 Sch-M Whether authorized packaging instructions for each product of various pack size and type are maintained and complied wi

34.2 Sch-M Specify whether all material, equipment, rooms

and packaging lines are labelled with an indication of
product being processed with batch no.

34.3 Sch-M Whether packaging lines are independent and adequately segregated.

34.4 Sch-M How line clearance is performed. Whether records of line clearance is maintained according to appropriate checklist.

34.5 Sch-M Do the packaging materials arrive on a covered trolley?

34.6 Sch-M Are packaging materials verified against a master set to ensure that they are the most recent edition and the correct materia

34.7 Sch-M Are the quantities of packaging materials verified against the amounts stated as dispensed from the warehouse?

34.8 WHO TRS- Specify the monitoring code (bar code, pinholes etc.) for final packing materials.
986

34.9 Sch-M Is the batch yield calculated immediately upon completion of packaging operation & prior to the introduction of a new bat

34.1 Sch-M Is the yield calculation independently verified by second individual and whether any significant deviation from accepted y

34.11 Sch-M Is any excess printed packaging material destroyed on completion of the batch?

34.12 Sch-M Is there a provision in the department for the separation of printed packaging material for destruction & rejected product?

34.13 Sch-M Whether Batch packaging record covered all the

34.14 WHO TRS- Whether Batch packaging record covered all the points as prescribed in WHO-TRS 986 & PIC/S
986

34.15 Sch-M Whether all the documents generated during packaging are attached with the Batch packaging record.
34.16 Sch-M Whether BPR are based on current master formula record.

35 Standard Operating Procedure and Records: -

35.1 Sch-M Verify the List of SOPs and mention total number of SOPs followed by the firm.

35.2 Sch-M Has all the SOPs been displayed.

35.3 Sch-M The formats, logs & SOPs are current

35.4 Sch-M Is any obsolete copy seen in the Area?

36 Reprocessing and Recoveries:-

36.1 Sch-M Verify the SOP for reprocessing.
36.2 WHO TRS- Whether reprocessed batch is subjected to stability evaluation.
986

36.3 Sch-M Whether the recoveries are added into the subsequent batches. If yes specify the procedures.

37 Finished Product:-
37.1 Sch-M Specify whether finished products are held in quarantine until their final release.

37.2 Sch-M Specify the storage arrangement of finished products after final release by QA

38 Quality Control Area: -

38.1 Sch-M Specify whether QC area is independent of production area.

38.2 Sch-M Specify the working space provided for QC:

38.3 Sch-M Specify the procedure followed for approval/rejection of raw materials, packaging materials, intermediate products and fin

38.4 Sch-L1 Specify the arrangement provided to protect sensitive electronic balances from vibrations, electrical interference, humidity

38.5 Sch-L1 Specify the safety measures taken to avoid any accidental hazards in the QC department.

38.6 Sch-M Specify whether separate washing and drying area is provided for glassware
38.7 Sch-L1 Specify which grade of glassware is used in assay procedures and whether they are certified/calibrated. Verify the certifica

38.8 Sch-M Specify whether any particular test is outsourced. If so mention the name of laboratory and verify the contract made in this

39 Microbiology Lab
39.1 Sch-M Whether separate AHU's are provided for microbiological testing areas.

39.2 Sch-M Whether support areas are under same AHU

which is used for sterile area.

39.3 Sch-M Briefly describe layout of the microbiology lab

(attach copy of the layout if available)

39.4 Sch-M Whether entry to the sterile area is through three air lock systems with separate exit

39.5 WHO TRS- Specify whether access in sterile area is controlled, and if so the system followed in this regard
986

39.6 Sch-M Verify the list of equipment used in the microbiological lab and also specify whether these are placed logically and functio

39.7 Sch-M Specify whether operators are trained in gowning procedures. Verify the training records.

39.8 Sch-L1 Specify the gowning procedure to enter the sterile area. Verify the entry and exit records.

39.9 Sch-L1 Specify the air class of sterile areas and whether pressure difference is maintained. Verify the records.

39.1 WHO TRS- Specify whether an environmental monitoring programme is followed with alert and action limit.
986
39.11 Sch-M Specify whether a documented cleaning and disinfection programme is in place.

39.12 WHO TRS- Specify whether a procedure for dealing with spillages in sterile area is in place.
986

39.13 WHO TRS- Whether separate areas provided for sterility testing, assay of antibiotics & vitamins and MLT in sterile area.
986

39.14 Sch-M Specify the type of workstations (LAF) provided in the sterile area.

39.15 Sch-M Whether double door autoclave is provided for transferring of materials from unclassified area to sterile area.

39.16 WHO TRS- Verify the area qualification document for sterile area.
986
39.17 WHO TRS- Verify the procedure for selection of sampling location and interpretation of results for environmental monitoring of steril
986

39.18 Sch-L1 Specify whether qualification of all equipment and instruments used in this department is covered under VMP.

39.19 Sch-L1 Verify the qualification document of major equipment like autoclave/incubator, hot air oven, refrigerator, LAF etc.

39.2 Sch-L1 Specify the Calibration procedure of temperature measurement devices used in autoclave and incubator. Verify whether it

39.21 Sch-M Verify the procedure for the handling and disposal of chemical and microbial waste.

39.22 WHO TRS- Specify the procedure followed to verify the validity of the test in case of antibiotic potency testing.
986
39.23 WHO TRS- Specify whether there is separate autoclave for decontamination.
986

39.24 WHO TRS- Specify whether the Vendors for dehydrated media is approved and qualified.
986

39.25 WHO TRS- Specify whether GPT is carried out for dehydrated media.
986 / IP

39.26 Sch-L1 Specify whether performance of culture media (recovery or survival maintenance) is carried out and the results meet accep

39.27 Sch-L1 Specify the source of procurement of reference culture and its maintenance.

39.28 Sch-L1 S pecify the Air Grades for following areas:

39.29 Sch-M V erify the following records:

39.3 IP Verify how the concentration of the inoculums is determined.

39.31 Sch-M Whether firm has provided microbiology lab for MLT test for nonsterile dosage form. If no how this test is complied.

40 Quality Control System: -

40.1 Sch-L1 Specify the source of procurement of various reference standards

40.2 Sch-L1 How the reference standards are stored, evaluated and maintained.
40.3 WHO TRS- Specify whether authorized access system is followed for reference standards.
986

40.4 Sch-L1 Verify the SOP and records for preparation of

working standard from the reference standard.

40.7 Sch-M Specify whether approved specifications are

available for all:

40.8 Sch-L1 Verify whether all approved specifications are

based on validation.
40.9 WHO TRS- Is there any SOP for handling of OOS product (out
986 of specification)?

40.10 WHO TRS- Specify the procedure for review of test data &
986 calculations.

40.11 Sch-L1 Specify whether a designated person is

responsible for receipt of samples for testing.

40.12 Sch-L1 Specify the procedure followed for receiving and

recording (logging in). Verify the SOP and records

40.5 Sch-L1 Verify the SOP and records for destruction of

unused working standard

40.6 Sch-M Verify the sampling SOPs and records for:

40.13 Sch-L1 Specify the procedure for storage and distribution of received samples to different analyst.
40.14 Sch-L1 Is there a maximum time limit for retention of sample in the laboratory prior to testing?

40.15 Sch-L1 Specify the procedure followed for preparation, consumption & destruction of volumetric solution. Verify the SOP and re

40.16 Sch-L1 Specify whether there is a log book for the preparations of the reagent including name of the analyst, name of the reagent,

40.17 Sch-L1 Specify the procedure followed for using GR, LR and AR grade of chemicals / solvents used for calibration & sample test

40.18 Sch-L1 Specify whether respective STP is followed by the analyst for analysis.

40.19 Sch-L1 Specify the procedure of reporting the result of analysis by the analyst to QC Head.

40.2 Sch-L1 Specify the procedure followed for storage of samples after testing.

40.21 Sch-L1 Specify the procedure for retention of samples after testing is completed.

40.22 Sch-L1 Specify the procedure followed for issuance of

COA.

40.23 Sch-L1 Specify procedures for safe removal of waste from the laboratory.
40.24 Sch-M Specify whether raw materials, intermediates and
finished product testing is carried out as per specifications and
raw data is maintained.

41 Analytical Method Validation (AMV):-

41.1 IP Specify whether following Characteristics are
considered during validation of analytical methods:

42 HPLC Calibration
42.1 IP Verify the records of calibration of following
parameters:

(GPV).

43 Dissolution Apparatus Calibration

43.1 IP Verify the records of calibration of following
parameters:

the vessel & paddle

the vessel & Basket

stop watch

[Verify whether dissolution is calibrated

against standard prednisolone tablets]

44 UV-VIS
44.1 IP Verify the records of calibration of following
parameters:

visible wavelength

46 FTIR
46.1 IP
pa

47 TOC Analyser+
47.1 USP
pa

48 Stability Studies
48.1 Sch-M Specify whether stability study is carried out in the QC and if so, is there separate area for Stability Chamber for stability s
48.1 Sch-M

Specify whether shelf life of the product is fixed on the

basis of stability studies.

48.2 WHO TRS- Verify the qualification documents of all the stability chambers.
986
48.3 WHO TRS- Specify whether a written programme for ongoing stability determination is in place.
986
48.4 WHO TRS- Specify whether a complete description of stability study is available.
986
48.5 WHO TRS- Verify the stability calendar along with stability protocol and documents. Attach the copy of stability calendar
986

48.6 WHO TRS- Specify whether the stability protocol indicates complete set of testing parameters and methods.
986

48.7 WHO TRS- Specify whether summary of all generated data from the study are retained.
986
48.8 WHO TRS- Specify the testing schedule for each product
986
48.9 WHO TRS- Specify whether stability study is performed after any significant changes in process equipment, packaging materials etc.
986

48.1 WHO TRS- Specify the validation method for stability chambers
986
48.11 WHO TRS- Specify the Temperature and humidity for real times studies carried out for fixing shelf life of drug in the country.
986

Verify the records of calibration of following

rameters:

Verify the records of calibration of following

rameters:

49 Quality assurance:-
49.1 Sch-M Mention the documents prepared and maintained by QA department

49.2 Sch-M Specify the responsibility of the QA Head.

49.3 Sch-M Specify the procedure followed by QA department to ensure the implementation of all SOPs in the plant.

49.4 Sch-M Verify the total list of SOPs maintained by QA and how QA ensure that no obsolete SOP is in circulation.

49.5 WHO TRS- Specify whether any procedure is followed for preparation of SOPs and its circulation to all concerned. How master, contr
986

49.6 WHO TRS- Mention the change control procedures & examine three recent change control forms.
986
49.7 WHO TRS- Specify the procedures followed to ensure CAPA process. Verify the SOP and three recent records in this regard.
986

49.8 WHO TRS- How deviation are controlled. Verify SOP and three recent
986 deviations. Specify whether all deviations
are reported and records maintained.

49.9 Sch-M Is the production batch record and release test results reviewed for accuracy and completeness before a batch/lot of finishe

49.1 Sch-M Verify the checklist and SOP in this regard.

50 Annual Product Quality Review (APQR):-
50.1 WHO TRS- Specify Whether Annual Product Quality review is
986 carried out for each product
50.2 WHO TRS- Specify whether following criteria are considered
987 for review:

results;

methods;

and any adverse trends

and the investigations performed at the time

actions on product process or equipment

and utilities e.g. HVAC, water, or compressed

gases

50.3 WHO TRS- Verify whether Cp and CpK values are calculated
988 and what is the acceptance criteria fixed.

51 Product Recalls:-
51.1 Sch-M Specify the product recall system.
51.2 Sch-M Verify the procedure followed to handle the
recalled products
51.3 Sch-M Are distribution records available for a prompt
recall of products from the market?

51.4 Sch-M Verify the SOP for recall of products clearly

defining responsibility, procedure reporting,
reconciliation etc.
52 Complaints and Adverse Reactions:-
52.1 Sch-M Are complaints, whether received in oral or written
form, documented in writing, and retained in a designated file?

52.2 WHO TRS- Are complaints reviewed on a timely basis by the

988 Quality Assurance unit?
49.11 Sch-M Whether QA is involved in control of starting
materials, intermediate products, bulk products,
process controls, calibrations, validation and
release of finish goods.

52.3 WHO TRS- Is CAPA process followed in response to each complaint documented?
988
52.4 WHO TRS- Specify whether system of route cause analysis is followed by the firm on the complaint of adverse drug reaction.
988

52.5 Sch-M Specify the review system for complaints concerning the quality of products.

52.6 Sch-M How records of complaint and adverse reactions maintained.

52.7 Draft Rules Whether the firm has provided Pharmacovigilance department for analysing complaints of adverse drugs reactions resultin
52.8 Sch-M Are there any criteria for action to be taken on the basis of nature of complaint / adverse reaction?

53 Site Master File:-

53.1 Sch-M Whether all the relevant information has been included in the site master file.

53.2 Sch-M Whether quality policy has been included in the site master file.

53.3 Sch-M Verify whether all information as per schedule M

53.4 WHO TRS- Verify whether all information as per WHO TRS
988 986 and PIC/S document.
54 Validation
54.1 WHO TRS- Specify the validation policy of the company
988
54.2 WHO TRS- Whether a Validation Master Plan has been prepared.
988
54.3 Sch-M Verify resources and those responsible for its implementation.

54.4 WHO TRS- Identify the systems and processes to be validated as per VMP
988
54.5 WHO TRS- Verify whether documentation, standard operating procedures (SOPs), Work Instructions and Standards (applicable for na
988

54.6 WHO TRS- Validation list for facilities/equipment, processes /

988 procedure and products.
54.7 WHO TRS- Specify whether key approval criteria are mentioned in the VMP & how record and conclusion of such validation studies a
988

54.8 WHO TRS- Verify Protocol format for each validation activity, including re-validation and reasonable unforeseen events (power failur
988

54.9 WHO TRS- Whether validation calendar is specified in VMP.

988
54.1 Sch-M Specify whether the critical processes validated
Prospectively, retrospectively or concurrently.

54.11 WHO TRS- In case electronic data processing systems are used, are these validated?
988
54.12 WHO TRS- Please specify whether periodical challenge tests performed on the system to verify reliability.
988

54.13 Sch-M Are the validation studies performed according to pre-defined protocols?

54.14 Sch-M Is a written report summarized, results and conclusions prepared and maintained?

54.15 WHO TRS- Is the validity of the critical processes and procedures established based on a validation study?
988

54.16 WHO TRS- Are criteria established to assess the changes originating a revalidation?
54.16 Are criteria established to assess the changes originating a revalidation?
988
54.17 WHO TRS- Are trend analyses performed to assess the need to re-validate in order to assure the processes and procedures continue to
988

55 Internal Quality / GMP Audit Programme

55.1 Sch-M Does a formal auditing function exist in the Quality
Assurance department?

55.2 Sch-M Does a written SOP specify who shall conduct audits and qualifications (education, training, and experience) for those wh

55.3 Sch-M Does a written SOP specify the scope and frequency of audits and how such audits are to be documented?

55.4 WHO TRS- Specify whether record is maintained for CAPA on the basis of self quality audit / inspection and whether same is reviewe
988

56 Pharmaceutical Development

56.1 ICH/Q-8- Whether there is Research and Development facility available.

PICS
56.2 ICH/Q-8- Whether formulation development facility up to development of exhibit batches available.
PICS

56.3 ICH/Q-8- Whether firm hires consultants for technology transfer. If so details thereof.
PICS
56.4 ICH/Q-8- Whether firm has adopted latest tools (quality by design) to develop new products.
PICS

57 Quality Risk Assessment System:-

57.1 ICH/Q-9- Whether the firm has adopted QRM principle to mitigate risk involved in pharmaceutical development, manufacturing and
PICS

57.2 ICH/Q-9- Whether firm has policy document on QRM. Specify document number and its effective date.
PICS

57.3 ICH/Q-9- Which known principles have been adopted to analyse risks e.g. FMEA, HAZOP, HACCP, FTA etc.
PICS

57.4 ICH/Q-9- Whether risk priority number (RPN) is calculated based on severity, probability and detectability. If so, what is the criteri
57.4 Whether risk priority number (RPN) is calculated based on severity, probability and detectability. If so, what is the criteri
PICS

57.5 ICH/Q-9- How many products, process etc. have been analysed for risk. Give brief.
PICS

58 Data Integrity
58.1 Sch-M Whether the records are completed at the time of the operation and are legible maintained with raw data if applicable.

58.2 Sch-L1 Whether the firm has software based manufacturing and testing equipment

58.3 Sch-L1 Whether the individuals are provided log in IDs for access. All login and logout information should be available.

58.4 Sch-L1 Whether rights to work, amend, modify, delete are specified in written document.

58.5 Sch-L1 Whether right to access and modify are with two different individuals. If yes how QA is involved in modification of data.

58.6 Sch-L1 Whether audit trails related to project creation (study creation), project (study) modification, deletion etc. are available.

58.7 Sch-L1 Whether the data is backed up at regular intervals. If yes what is the written back up policy. The data backup must be serv

58.8 Sch-L1 How Excel sheets are validated if calculation are done in Excel sheet.

58.9 Sch-L1 Whether the firm has QA SOP for review of data integrity or audit trail. If yes how the modification and deletions are revi

59 Pharmaceutical Quality Management System (PQS)

59.1 WHO TRS- Specify the management responsibility defined as per the quality manual
986
59.2 WHO TRS- Specify the Procedures followed for continual improvement of process performance and product quality
986

59.3 WHO TRS- Specify the performance indicators presently followed by the firm to monitor the effectiveness of PQS like product quality
986

59.4 WHO TRS- whether purchases are also included under PQS
987
59.5 WHO TRS- Specify whether life cycle approach is followed
986
59.6 WHO TRS- Give synopsis of last to management review meeting held by the firm
986
Critical Observations:
 CLASSIFICATION

OF CRITICAL FINDING
S. No. Subjects Types of findings
1 Building and premises 1) The manufacturing facilities for potent drugs such as sex
hormones, beta-lactam and cytotoxic are common with
general drugs.
2) Some of the critical areas of manufacturing are exposed
directly with the environment
3) Pest infestation, rodents and birds found in the
manufacturing premises
4) No AHU is provided in the manufacturing areas where
raw materials and/or products are exposed.

5) There are open drain(s) in the critical areas where the

products are exposed.

2 Water and compressed air systems 1. Potable water was found outsourced without any
records / validation regarding any further treatment and / or
analysis before use.
2. WFI system and pure steam system of parenteral unit are ill
maintained and data in respect of their quality is falsified.
3. Purified water system is ill maintained and data in respect
of its quality is falsified.
4. Unfiltered gases used during filling of injectable or eye
preparations

3 Ware housing area. Storage condition was found unhygienic with

accumulation of dust, dirt, pest manifestation, fungal growth,
water stagnation and materials dumped without any
identification labels.
 4 Precautions against mix-up and cross 1) Processing of sensitive drugs like Beta lactam
contamination Antibiotics and Sex Hormones was found carried out in the
same facility without independent AHU and proper pressure
differentials
2) Beta Lactam Antibiotics, Sex hormones and cyto- toxic
substances were found manufactured in a same facility without
any dedicated area with common arrangements for raw
materials store, sampling & dispensing operations.

5 Production area for sterile preparation Wide cracks on walls/floor/ceiling or fungal growth or cobwebs, or insects inf

6 Environmental Monitoring (Sterile preparation) 1. Suitable arrangements are not made for maintaining
temperature and humidity in critical areas.
2. The viable counts are not performed as per rules. The
microbial counts were found well above the limits however
reported within limits.
3. The HEPA filter integrity test (smoke testing),
particulate monitoring in air, air change rates tests are not
performed as per Rules.

7 Garments 1. Sterile garments are not used in aseptic area.

2. Unclean foot wears are used in critical areas.
8 Equipment 1) The sterilizers are not studied for heat distribution /
penetration. Effectiveness of sterilization process not
established by using microbial spore indicators.

2) The material of construction of the equipment is not suitable.

e.g., found rusted, cracked, leaking etc.

3) Media fill studies are not performed for aseptic products in

simulated conditions as per Rules.
4) Calibration data for the instruments / equipment is falsified.

9 Product Containers & Closures Recycled / second hand containers and closures are used for primary packaging

10 Others Batches failing initial sterility test are released for sale on the basis of a sec
.

11 Quality assurance 1) No QA function and QA head is not independent.

. 2) No QA procedure for reviewing of production batch record
and test results before product is released in the market
3) No written Master Formula Records.
4) No validation activity performed by QA

12 Complaints and Adverse Reactions 1) No procedure for complaint handling and

. complaints are not investigated and records are not maintained.

13 Site Master File SMF is not factual.

14 Data Integrity Data is not recorded on a contemporary basis/Records
. are not made at the time of actual activity and records are
completed later on arbitrarily. Falsification of data is observed.
15 Stability Studies No stability studies are performed either in-house or by
. way of outsourcing to assess the shelf life of the products before
marketing and the expiry date of the product is fixed arbitrarily

16 Technical personnel The critical activities of production and testing is

. carried out without the direct supervision of competent technical
staff.

17 Quality control Raw material testing, intermediate testing or finished

. product testing is not carried out and raw data was found
falsified
 RESPONSIBLE DEP.

Observations Rating CONCERN

DEPARTMENT

QA

HR & QA
 HR &QA

Engineering &QA

Storage
Area:

In storage
areas where
there is no QA
need for
detailed
visual
inspection or
reading, 2

Engineering &QA

HR & QA

HR,Engineering &QA

Engineering &QA

HR

HR
Engineering &QA

Engineering &QA

HR

HR

HR

HR

Engineering

Engineering

Engineering

Engineering &QA

Engineering &QA
Engineering &QA

Engineering &QA

Production, &QA

Production, &QA

Production, &QA

Engineering

Engineering

Engineering & QC
 Engineering & QC

Production, &QA

Engineering &
Ptoduction

Production, &QA

QC

Engineering

Engineering

Engineering

Engineering

Engineering

Engineering

Production/Engineering

Micro/QC

Store
 Store

Engineering
6

Micro/QC

QA

Engineering

Engineering

Engineering

Store

HR

HR

HR

HR

HR

7
 HR

Production

Production

Engineering

HR

QA

QA

QA

QA

QA

HR
8

Engineering &QA
Store & Engineering

Store

Store

9
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ON

DINGS
ACCONTABLE DEP.

ACCONTABLE DEP.

QA

QA
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QA

QA

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HR

HR
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HR

HR

HR

HR

QA

QA

QA

QA

QA
 QA

QA

QA

QA

QA

QA

Engineering &QA

QA
QA

QA

QA

QA

QA

QA

QA

QA

QA

QA

QA

QA

QA

QA
QA

QA

QA

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HR

HR

HR
HR

QA

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HR

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QA