Gmp Checklist

British Standards Institution

BSI CHECK LIST FOR WHO GMP INSPECTION

1.

GENERAL:

1.1

Date of Inspection 25th to 28th March 2008.

1.2

Name of the company Hindustan Latex Ltd. Plot No. 16 A/1 CSEZ, Kakkanad, Cochin – 682 037

1.3

Organizational chart of the Company (attach a copy) Copy attached as Annex 1 Categories of Drugs / Products Manufactured Female Condom (Nitrile Latex- Lubricated)

1.4

Do the firm/ company have a written quality policy? If yes, obtain a copy of the Same and attach. YES . Copy attached as Annex 2

1.5

Names of the members of the inspection team

NAME

DESIGNATION

1. VIJAY KUMAR MAGAN

Team Leader

2. S. MADHAVAN

Team Member

3. ------

----

GMP Checklist Rev 0

SIGNATURE

British Standards Institution

2.

PERSONNEL

(i)

Name of Incharge

Qualification

a) Mr. G.Krishna Kumar B -Tech (Unit Chief) b) Mr. Mahesh Kumar P. R B -Tech (Unit In Charge) c) c) Mr. Rajesh G Joseph B -Tech ( Production) d) Miss. Lijy T K M -Tech (Quality Control) e) Mr. A. Muraleedharan M-Tech f) Ms. Smitha B-Tech / MBA g) Mr. Venugopalan B-Tech

Whether Approved or not

Present/ absent

yes

present

----

present

----

present

----

present

-------------

present present present

(ii)

Number of Production Supervisors. Mr.ALBY

(iii)

Number of Analysts QA staff. Mr. Lawrence and Mr. Sajith

(iv)

Are Production and quality functions independent of each other? Yes

(v)

Are all sections adequately staffed (Supervisor / Asst. Mfg. Chemist) taking into Consideration the work load?

(vi)

(vii)

Yes. Testing personnel needs to be FDA approved. Is recruitment of an employee preceded by medical examinations? Yes. Recruitment of employee could be preceded by medical check-up instead of a certificate of physical fitness What is the periodicity of subsequent medical examinations? Once a year (Reference – site master file: Section 2. Personnel; sub-section 2.4 Health Requirement)

(viii) Is an employee whose state of health is doubtful immediately removed from work site until he is fully recovered? Yes. (Reference – site master file: Section 2. Personnel; sub-section 2.4 Health Requirement) GMP Checklist Rev 0

British Standards Institution

(ix)

Do all personnel receive WHO GMP's training? Yes. (Training included revised schedule M requirements of FDA pertaining to GMP, and ISO 13485:2003) (x) Is training documented? Yes (xi) What is the periodicity of training? As the unit started in Nov 2007, only one training has been carried out in 2007. (xii) Are protective steps against likely damage to health due to occupational hazards satisfactory? Generally yes. However, chairs used by various operators at visual checking, electronic testing, etc.., needs to be ergonomically designed. Currently make-shift arrangement is being made.

S.NO. CATEGORIES

COMPLIANCE Y/N/NA

REMARK/ COMMENTS

3.

PREMISES

(i)

Are there are source of pollution in the neighbourhood of the building?

N

East – Road South – Road West – Software North - Road

(ii)

Is plant layout of suitable size design & construction sufficient for production and quality control of drug being produced?

Y

Site master file is maintained

(ii-a)

Any open drain, blocked sewer or public lavatory nearby?

N

No drains inside the production area.

(iii)

Is there adequate space for equipment, material and movement of personnel and material?

Y

(iv)

Is there any programme to check entry of birds, rodents and insects?

Y

(iv-a)

Are any products other than drugs manufactured in the GMP Checklist Rev 0

N

Procedure CEZF 28 includes pest and rodent control. Procedure / Program may include control for entry of birds and insects

British Standards Institution

same building? CEZF28

(v)

Are buildings and facilities properly constructed to facilitate adequate cleaning and sanitization?

Y

(vi)

Are lighting and Ventilation adequate?

Y

(vii)

Are facilities for changing street clothes, footwear, washing and toilets adequate and satisfactorily maintained?

Yes (Partially)

Facility for changing street clothes, footwear for visitors may be considered.

(viii)

Are sewage, trash and other effluent disposal adequate?

Y

Discharged into common sewage treatment plant

(ix)

Whether production of other specified products like hormones, cylotoxic drugs segregated or whether production is carried out on campaign basis.

NA

(x)

State of maintenance of building (Check whether the firm/company have preventive maintenance programme)

Y

GMP Checklist Rev 0

Organization may consider maintenance program for building with respect to painting, etc., Building stability certificate as per Indian Factories Act could be done.

British Standards Institution

(xi)

Are floors, walls and ceiling properly constructed and easy to clean, maintain and disinfect?

Y

Requirements of Schedule M-III of Drugs and Cosmetics Rules 1945 for buildings could be followed.

(xii)

Is there any programme for general housekeeping?

Y

CEZF09

COMPLIANCE Y/N/NA

REMARK/ COMMENTS

S.NO. CATEGORIES 4.

STORAGE OF STARTING MATERIALS

(i)

Are there physically segregated areas for Raw materials? Packaging

N

(ii)

Is there quarantine area for incoming raw material?

Y

(iii)

Is there segregated area for rejected material?

Y

(iv)

Are there separate areas for material requiring special storage conditions e.g., controlled temperature? Flame proof? GMP Checklist Rev 0

NA

No Physical segregation of RM & PM areas. These are stored in the same room with proper area identification.

Quarantine/ Rejected material is part of finished good area. A separate quarantine area could be considered.

British Standards Institution

(v)

Are the areas adequate for storage of the materials in relation to their amount and facilities provided?

Y

Adequate for current level of single shift production

(v-a)

Do all containers of active RMs excepients and intermediates bear appropriate labels at all stages of manufacture? If no, give details

Y

Labels available for all stages

(v-b)

Are empty containers freed of old labels and checked immediately prior to use?

NA

(vi)

Is lighting and ventilation adequate in warehouse?

Y

(vii)

Have the areas requiring special storage conditions provided with monitoring devices and data maintained?

Y

(viii)

Is there any programme for general housekeeping?

Y

(ix)

Is there any evidence of entry of insects, rodents & birds?

N

(x)

Are there warehousing operating instructions?

Y

(xi)

Are these instructions being followed?

Y

(xii)

Are there labels for materials of different status i.e., quarantine, tested and released for use and rejected?

Y

(xiii)

Are there labels of different colours?

Y

GMP Checklist Rev 0

Temperature and humidity meters are provided

S.O.P evidenced. Ref. CEZF 25 White accepted; Pink – rejected; Yellow Quarantine

British Standards Institution

S.NO. CATEGORIES (xii-a) Are labels on containers of RMs to be used in manufacture checked with regards to identity, quantity, & QA approval? If no, give details. (xiv)

Are there the following information on labels? name of material? Batch number? Analysis number? Date of release/ rejection? Date of expiry? Date of testing?

COMPLIANCE Y/N/NA Y

Y Y N Y Y N

Is the sampling performed by Qualities Control personnel?

Y

(xvi)

Are there sampling procedures?

Y

(xvii)

Are there the following information of each sample taken?

(xv)

GMP Checklist Rev 0

REMARK/ COMMENTS

Date of testing in incoming material record

CZEF08, CEZF23 CZEF08

British Standards Institution

-

Name of person who performed sampling? Number of samples taken? Number of containers sampled Date of sampling?

Y Y Y Y

(xviii) Are the containers provided for storage of raw materials suitable to preserve the quality?

Y

(xix)

Is there stock rotation programme (i.e., FIFO)?

Y

(xx)

Are the printed packaging material stored in orderly manner and well separated to prevent mixing?

Y

(xxi)

Are they recorded on stock cards/registers?

Y

(xxii)

Are enclosed and locked areas provided for storage of narcotic or highly toxic drugs?

NA

(xxiii) Is exterior storage available: Solvent storage area? Inflammable material storage area? Whether safety measures provided have been assessed by regulatory agency if any? Are SOP’s available for handling of these materials?

S.NO. CATEGORIES

NA

COMPLIANCE Y/N/NA

REMARK/ COMMENTS

Separate area provided

WEIGHING AREA

(i)

Is the weighing area segregated?

Y

(ii)

Are lighting and ventilation adequate?

Y

(iii)

Is the area clean?

Y

(iv)

Do the personnel wear appropriate clothing?

Y

(v)

Is there danger of cross contamination during weighing?

N

(vi)

Are the scales & balance calibrated regularly and records maintained?

Y

Are the containers of the raw materials to be weighted, GMP Checklist Rev 0

CEZF26

NA NA NA

5.

(vii)

CEZF26

CEZF32R01 Y

British Standards Institution

cleaned before opening? (viii)

After weighing, are these containers sealed?

Y

(ix)

Are the raw materials for each batch, after weighing properly identified?

Y

(x)

Are adequately clean and dried equipments used for dispensing materials from the containers?

Y

6.

EQUIPMENT

(i)

Is the equipment adequate for intended use? (State size, capacity and check batch size)

Y

(ii)

Is it constructed in such a way that lubricants coolant, etc. cannot contaminate the drug product?

Y

(iii)

Does the equipment permit cleaning and maintenance?

Y

(iv)

Does the equipment show its status i.e., clean, dirty, batch contents?

Y

(iv-a)

Do all apparatus/equipment bear appropriate labels to identity the product for which the equipment is used, its batch no., date, etc.?

(v)

Are SOPs available for cleaning , maintenance and sanitization

GMP Checklist Rev 0

NA

Y

CEZF27

British Standards Institution

S.NO. CATEGORIES

COMPLIANCE Y/N/NA Y

REMARK/ COMMENTS CEZF 27 CEZF27

(vi)

Are log books maintained for cleaning, maintenance and sanitization of major equipment?

(vii)

Are SOPs readily available to operators?

Y

(viii)

If automatic electronic or mechanical equipment is used, are there? Written programmes for calibration/ inspection. Records of such programmes? Checks to ensure that any changes are made only by authorised person?

Y Y Y Y

CEZF32 CEZF32R01, CEZF32R02

The condensing units of air conditioners are installed in finished goods storage area leading to increase in storage room temperature beyond 35*C required for the storage of finished goods.

7

FACILITIES AND UTILITIES

(i)

Are air handling units adequate and properly located and functional?

Y

(ii)

Is air conditioning system adequate and functional?

Y

(iii)

Are steam generation facilities adequate and functional?

NA

(iv)

Are vacuum system adequate and functional?

Y

(v)

Is compressed air system adequate and properly functioning?

Y

(vi)

Is water supply system adequate? Check whether MC or Tube well supply. If tube well supply, whether potable?

Y

GMP Checklist Rev 0

For package sealing

British Standards Institution

(vii)

Is distilled water qualities and supply system adequate?

NA

(viii)

Is demineralised water quality & supply system adequate?

NA

(ix)

Sanctioned power ____________

Y

60 KW

(x)

Generator ______________ KVA provided

N

No generator is provided.

COMPLIANCE Y/N/NA

REMARK/ COMMENTS

Y N N Y Y

Cleaning schedule might include walls and ceiling apart from floor, door, windows, etc.,

S.NO. CATEGORIES 7-A

SANITATION AND HYGINE

(i)

Are cleaning schedule available for: - floors? - walls? - ceiling? - doors & windows? - electrical fittings? For different sections.

(ii)

Are SOPs available for cleaning & sanitization?

Y

CEZF09

(iii)

Are disinfectants used rotated?

Y

CEZF09

(iv)

Is microbial load monitored in different sections?

N

(v)

Is microbial load monitored in different sections?

N

Bio-burden test conducted at packed stage

(vi)

Are adequate facilities available for personal hygiene before entering into production area?

Y

(vii)

Are personnel instructed to observe personal hygiene?

Y

CEZF28

GMP Checklist Rev 0

British Standards Institution

(viii)

Are clean protective clothing provided to personnel?

N

(ix)

Are clean sterile protective clothing changed every time a person enters sterile area?

NA

8.

PRODUCTION AND IN-PROCESS CONTROL

(i)

Is there master production document for each drug product being produced?

(ii)

Are alterations to processes recorded and authenticated by Y competent authorized persons?

(iii)

Is the addition of components verified by another person?

Y

(iv)

Is an appropriate in-process control being performed?

Y

CEZF20

(v)

Are non sterile products tested for microbial load & whether microbial load is less than limits recommended by WHO?

Y

CEZT015

COMPLIANCE Y/N/NA NA

REMARK/ COMMENTS

S.NO. CATEGORIES

Y

(vi)

Are adequate measures taken to prevent cross contamination during production of different products in the same facility?

(vii)

If drying ovens are used: - Whether one product is dried at one time?

N

Are instrument used for temperature, pressure or other recording calibrated periodically and records maintained.

Y

(viii)

(ix)

Are semi-finished products stored properly and are identified?

Y

(ix-a)

Is stage of manufacture clearly indicated on containers?

Y

GMP Checklist Rev 0

CEZF 11

CEZF32R01, CEZF32R02

British Standards Institution

(x)

Is quality of water monitored? The following points may be checked? source of water? Is it potable? In case de-ionized water source of feed water? Frequency of charging columns sampling frequency? In case of water for injection information like: Is it prepared by distillation or reserve osmosis? Whether storage temperature is maintained at not less than 800C and circulated?

Y

(xi)

Do the containers and closures meet required specification?

Y

(xi-a)

Are containers checked for cleanliness and suitability for packaging before use?

Y

(xi-b)

Are containers of intermediates FPs intended for use in the plant closed property?

Y

(xii)

Is homogeneity maintained during filling of ointment, creams and lotions?

NA

(xiii)

Are the following controls carried out during filling operations: checks of column, weight or counts? Visual inspection of empty and filled containers? Visual inspection of closures?

Water is supplied by CEZ who monitor the quality of water.

CEZF08

S.NO. CATEGORIES

Y Y Y

CEZF23

COMPLIANCE Y/N/NA Y

REMARK/ COMMENTS Only one line exist

(xiv)

Is there adequate separation of packaging lines to prevent mix-ups?

(xv)

Is each line identified with name of the product, batch no. and packaging size?

Y

(xvi)

Is there only one batch of product on packaging line at any given time?

Y

(xvii)

Is an inspection carried out of each packaging line before labeling and packaging operation? GMP Checklist Rev 0

Y

British Standards Institution

(xviii) Is the inspection verified by quality control?

Y

(xix)

Is significant discrepancy in actual yield investigated?

Y

(xx)

Is inspection carried out of each packaging line after operation to ensure that all excess/rejected labeling material are removed?

Y

(xxi)

CEZF10

Are all excess or rejected coded labels and cartons destroyed?

Y

Is batch production record prepared for each batch of product and maintained?

Y

(xxiii) Do the batch production records indicate that each significant step in manufacturing was performed and checked by second individual wherever appropriate?

Y

(xxiv) Are master instruction or procedures being followed?

Y

Are these instruction and procedures being followed?

Y

(xxii)

(xxv)

CEZF 21 CEZF23 CEZF23 R10

(xxvi) Are only materials, containers and appliances necessary for the job in hand stored in the vicinity of the manufacturing areas and are these properly labeled with name of the product, batch no.. date, etc.

Y

S.NO. CATEGORIES

COMPLIA NCE Y/N/NA

9.

PRINTED LABELLING AND PACKAGING MATERIAL CONTROL

(i)

Is specimen copy of each label and printed packaging material approved before sending it to the printer?

GMP Checklist Rev 0

Y

Provided in SOP

REMARK/ COMMENTS

British Standards Institution

(ii)

Are label and other printed packaging material checked and approved by quality Control before release to production.

Y

CEZF08

(iii)

Is access to labels and other printed packaging material store limited to authorized persons?

Y

CEZF 45

(iv)

Are there any designated individuals to control and issue labels and other printed packaging materials?

Y

CEZF 45

(v)

Are individual labels stored separately?

Y

(vi)

Are printer’s count accepted or counted by factory worker for inventory purposes?

Y

(vii)

Do batch production records indicate: Number of labels or other printed packaging materials to be issued? Batch or control code? Reconciliation of number/ amount of labels and printed packaging materials issued, used and destroyed?

Y Y Y Y

CEZF 45

10.

QUALITY CONTROL

(i)

Are master control procedures: Signed and dated by responsible persons?

Y

Do these control procedures include specifications, test procedures or other control procedures for: Raw materials? In-process materials? Packaging and labeling materials? Finished products?

Y Y Y Y

CEZF 08 CEZF 20

Y

Provided in SOP

COMPLIA NCE

REMARK/ COMMENTS

(ii)

(iii)

Are the procedure in written form and readily available to QC personnel?

S.NO. CATEGORIES GMP Checklist Rev 0

CEZF23

British Standards Institution

Y/N/NA Y

CEZF12

Are there written sampling procedures for: raw materials? Packaging and labeling materials? Finished products?

Y Y Y

CEZF 08 CEZF 20 CEZF 23

(vi)

Are samples collected by QC personnel?

Y

(vii)

Is there special room for microbiological and sterlity testing?

NA

(viii)

Is the environment of room controlled?

Y

(ix)

Cultures, Sub cultures: - Are microbial strains obtained from authorized / reputed source? - Frequency of Sub-culturing. - frequency of identification of organism by microscopical or biochemical test - Are records of subculturing and identification of strain maintained

(iv)

Are there procedures and specifications for acceptance of reprocesses materials?

(v)

NA

(x)

Are animal test performed?

NA

(xi)

Are animal properly housed?

NA

(xii)

Are the temperature and humidity of animal house controlled?

NA

(xiii)

Are records of animals used maintained?

NA

(xiv)

Are the animal quarantined on receipt and examined for infection / disease?

NA

(xv)

Is access to animal house restricted to authorized persons? NA

(xvi)

Is fresh water and animal feed available in animal house?

NA

(xvii)

Are all raw materials , containers, closures, labels and printed packaging materials approved and released by QC for use in manufacture of drug product?

Y

GMP Checklist Rev 0

British Standards Institution

S.NO.

CATEGORIES

COMPLIANCE Y/N/NA Y

(xviii)

Are in-process controls carried out by QC personnel?

(xix)

Are semifinished products tested for appropriate tests when necessary?

Y

(xx)

Is bulk finished products tested for established specifications before packing?

NA

(xxi)

Is every finished products tested for established specifications before release for sale?

Y

(xxii)

Are there any deviations from established procedures or specifications and are these justified?

N

(xxiii)

Does the QC maintain records of all the test carried out?

Y

(xxiv)

Does the QC reviews all production and control records to ensure compliance with established written procedures before a batch of the products is released for sale?

Y

(xxv)

(xxvi)

Reference Standards: (a) Are reference standards (R.S.) available? (b) Are these primary or working R.S.? (c) Are working RS calibrated against primary R.S> or C.R.S.? (d) Are R.S. stored properly ( at low temperature under dehumidified conditions)? (e) Are records of R.S. and their calibration maintained? Are samples in sufficient quantity for testing twice retained of starting materials and finished products for future examination, in case of need?

(xxvii) Is written programme available for stability studies including the following: GMP Checklist Rev 0

REMARK/ COMMENTS CEZF20

CEZF23

CEZF23R10

Y

Y

Display boards available in production unit

Y

Retained samples for conducting all the test once is kept

Y

Stability study conducted by

British Standards Institution

-

Sample storage condition? Room temperature? Accelerated ageing test? Sample size and test intervals? Reliable and specific test methods? Testing in the same containers closure system in which it is marketed? Date and expiration date?

S.NO.

CATEGORIES

11.

STORAGE OF FINISHED PRODUCTS

(i)

F.H.C is referenced in the technical file.

COMPLIANCE Y/N/NA

REMARK/ COMMENTS

Is the area adequate with reference to materials stored?

Y

CEZF25

(ii)

Are lighting and ventilation adequate?

Y

(iii)

Whether special areas with temperature and humidity control required? Have these been provided?

Y

(iv)

Is there stock rotation programme (FIFO)?

Y

(v)

Are the inventory records to show: amounts? Batch number? Date of receipt?

Y Y Y

(vi)

Have distribution records been maintained?

Y

(vii)

Do distribution records provide sufficient information for drug recall purpose?

Y

Is there segregated area for retrieved goods?

Y

Are records available for retrieved goods?

N

No retrieved goods

Y Y

CEZF38 CEZF38, CEZF26 CEZF29 CEZF25 CEZF25

12. (i)

CEZF25R01

DOCUMENTATION Are SOPs available for the following: receipt of raw materials and other components? Quarantine and storage? Quality control system and approval/rejection? Release to production? Weighing and dispensing? Processing and production operations? GMP Checklist Rev 0

Y Y Y

CEZF25R01

British Standards Institution

-

S.NO.

Packaging and labeling? Quality control? In-process? Finished products? Storage of finished products? Distribution? Returned goods? Recalls and complaints? Cleaning and maintenance? Quality control of water? For reworking of nonconforming batches in existence? If yes, check records. CATEGORIES

Y Y Y Y Y Y Y Y Y Y Y Y

CEZF05 CEZF19 CEZF29 CEZF20 CEZF25 CEZF25 CEZF25 CEZF 43 CEZF43 CEZF09 CEZT 20 CEZF21

COMPLIANCE Y/N/NA Y

REMARK/ COMMENTS Provided in SOP

(ii)

Have these SOPs been prepared, signed and dated by responsible person?

(iii)

Are there additional documents like log books, notebooks or other similar records available to show execution of various functions?

Y

(iv)

In case of review and changes, are SOPs signed by responsible person and do these shoe their date of effectiveness?

Y

(v)

Are there records of receipt of raw materials and do these have following information? (Goods Receipt Note-GRN) Receiving GRN document number? Date of receipt? Supplier? Manufacturer? Manufacturer’s batch number? Type and size of containers? Number of containers and conditions?

(vi)

Are there records of stock and issue of raw material and do these have following information: Opening balance? Date of receipt Quantity received? Name and batch number assigned by the manufacturer? Invoice number, date, name and address of supplier? GMP Checklist Rev 0

CEZF11R04

Y Y Y Y Y Y Y

Y Y Y Y Y

QMS 04B

CEZF 38R01

CEZF 26R05

British Standards Institution

-

Analysis report number and date? Date of expiry Date of issue? Name and batch number of product for manufacture of which issued? Balance? Signature of issuing persons?

N Y Y Y Y Y

(vii)

Is there a master formulation record for each drug product being produced?

Y

(viii)

Is there a separate master production documents for each dosage form/ batch size?

Y

S.NO.

CATEGORIES

(ix)

Are these master production records signed and dated by competent person? Do they show the following particulars: the name, strength and description of the dosage form? Name and quantity of each active ingredient per dosage unit or per unit of weight or measure of the drug product? The total weight or measure of any dosage unit? A complete list of components identified by the name/codes? An accurate statement of the quantity of each component? Calculated excess of component, if any? Theoretical weight or measure at appropriate processing stage? Description of containers, closures and packaging materials? Complete manufacturing instruction? Sampling and testing procedures? Including in-process controls? Specifications and precaution to be taken?

COMPLIANCE Y/N/NA Y

(x)

Is a batch production record prepared for every batch produced?

(xi)

Is it reproduction of the appropriate master production GMP Checklist Rev 0

Y

One device being manufacture d for which dosage quantity of Silicone Oil is deined REMARK/ COMMENTS

CEZF11R01

British Standards Institution

documents or it has all critical information about the batch.

Y

(xii)

Has it been checked for accuracy signed and dated by a responsible person?

Y

(xiii)

Are the records maintained by QC for all the test carried out? Do these records include: graphs, chart, spectra, etc? calculations? Signatures of individuals who performed the test? Signatures of the designated person responsible for the review of records for accuracy and compliance with established standards?

Y

(xiv)

Are other associated records available?

Y

S.NO.

CATEGORIES

(xv)

Is documentation available readily for examination?

COMPLIANCE Y/N/NA Y

(xvi)

Where errors have been made in entering or transcribing data: Have errors been crossed out with one line? Have corrections been made above those crossed out? Are corrections dated and initialed?

(xvii)

Are batch production records capable of giving complete history of the batch right from the RM stage to the distribution of FP?

13.

CALIBRATION OF INSTRUMENTS AND MEASUREMENT SYSTEMS

(i) (ii) (iii)

Y Y Y

CEZF46RO1

Y

REMARK/ COMMENTS

Y

Y

CEZF11R01

Are the balances calibrated routinely?

Y

CEZF32R01

Have measuring equipments been calibrated?

Y

CEZF32R01

Y

CEZF32R01 CEZF32R02

Have thermometers/thermocouples been calibrated? (calibrated range) Minimum-25ºC Maximum-35ºC GMP Checklist Rev 0

British Standards Institution

(iv)

Have the pressure gauges been calibrated?

Y

(v)

Are instruments routinely calibrated?

Y

(vi)

What is the periodically of calibration?

Y

(vii)

Are records maintained for all calibration?

Y

Note:

Draw a list of all major instruments available and check calibration records?

14.

VALIDATION AND REVALIDATION

(i)

Are validation studies carried out for the following: Cleaning and sanitation procedures? Process? Testing?

6 months/ 1 year

List of instruments under calibration is maintained. CEZF 31

N Y Y

(ii)

Have qualification studies been carried out for equipment before validation studies?

Y

CEZF31

S.NO.

CATEGORIES

REMARK/ COMMENTS

(iii)

Are validation protocols available for validation studies?

COMPLIANCE Y/N/NA Y

(iv)

Do the validation reports show recorded results and conclusions?

Y

(v)

Are validation studies carried out periodically?

Y

(vi)

Is revalidation carried out in event of significant change in material (s) or equipment?

Y

Note:

Check a few qualification and validation studies in details:

GMP Checklist Rev 0

Only one validation carried out on 17.12.2007 Validation report 17.12.2007 checked.

British Standards Institution

15

COMPLAINTS

(i)

Are there written procedures for handling complaints?

(ii)

Is an investigation carried out wherever necessary including discussion with manufacturing personnel?

(iii)

Are complaints reviewed by QC?

(iv)

Is there a designated person for overall evaluation?

(v)

Are records maintained for complaints and do these include the following: name of the product with strength? Batch number? Name of complainant? Nature of complaint?

(vi)

Is a report of investigation made?

(vii)

Are complaints involving adverse reactions evaluated by qualified personnel?

(viii)

In case of significant adverse reaction, are appropriate Health Authorities notified?

16.

PRODUCT RECALLS

(i)

Is there written procedure for product recall in case of products known or suspected to be defective?

(ii)

Is there a designated person responsible for execution and coordination of product recalls? Y

S.NO.

CATEGORIES

(iii)

Have the degrees of recall been specified (i.e., Degree I, degree II and Degree III)

(iv)

Is the following information available? fax, telex, telephone number and addresses of national, regional and local regulatory GMP Checklist Rev 0

Y

Documented procedure for handling customer complaint CEZF 43.So far no customer complaints received.

Y

Documented procedure for product recall Ref. CEZT024 No product recall till date.

COMPLIANCE Y/N/NA

Y

REMARK/ COMMENTS Degree of recall not specified.

British Standards Institution

-

authorities? Fax, telex, telephone number and addresses of radio, television and press agencies? Fax, telex, telephone number and addresses of distributors, wholesalers, hospitals, etc.? Fax, telex and telephone numbers and addresses of competent authorities of the countries to which the drug products are exported?

(v)

Is there a system so that distribution records are readily available to the designated person responsible for product records?

Y

(vi)

Is the progress of product recalls recorded and final report issued including reconciliation between the delivered and recovered quantities of the product?

NA

(vii)

Is the effectiveness of product recall evaluated from time to time.

NA

(viii)

Is there a segregated area for recalled product?

N

No recalls reported.

No segregated area for recalled product considered in the lay-out. 17.

RETURNED AND SALVAGED DRUG PRODUCTS

(i)

Are written procedures available for receipt and control of returned products?

CEZT 23

(ii)

If a reason for returning the product implicates other batches is an investigation made and reports prepared?

(iii)

Are returned or salvaged drug products destroyed unless QC determines their reprocessing?

(iv)

Are records of returned products maintained including their disposition?

GMP Checklist Rev 0

Y No product returns reported

British Standards Institution

GMP Checklist Rev 0

British Standards Institution

S.NO.

CATEGORIES

(v)

Are there written procedures for reprocessing and do these include. Specifications and characteristics for approval? Identification of batch to reflect reprocessing? Revised stability data, if necessary.

18.

SAFETY

(i)

Is a safety manual available?

(ii)

Are safety equipments like helmets, shoes, goggles, glove, showers, aprons, masks, breathing apparatus, etc., available in the factory?

(iii)

Is adequate first aid equipment available at convenient place in the factory

(iv)

Is periodic first-aid training given to staff?

(v)

Are electrical connections, wiring etc. checked regularly?

(vi)

(vii)

Is flame- proof equipment used where flammable solvents or materials are stored or handled during manufacture?

COMPLIANCE Y/N/NA

REMARK/ COMMENTS

NA

Safety manual not available. However, emergency preparedness plan and response for fire and spillage is in place.

Y

Y

NA

Is adequate fire fighting equipment like fire extinguishers, ladders, fire buckets filled with water/ sand, etc., available?

Y

(viii)

Are staffs trained in fire fighting operation?

Y

(ix)

Is the building safe and provided with emergency exit, escape routes ladders, etc?

Y

Does the firm maintain accident history/record? If yes, comment on its adequacy.

Y

(x)

19.

POLLUTION CONTROL

(i)

Are arrangements for the following adequate?

(ii)

Disposal of solid/semi-solid waste? GMP Checklist Rev 0

NA

Necessary safety equipments are available Only fire extinguishers are provided.

Emergency exits in building must open outside

British Standards Institution

(iii)

Disposal of sewerage?

NA

S.NO.

CATEGORIES

(iv)

Disposal of liquid laboratory waste?

COMPLIANCE Y/N/NA NA

(v)

Management of gaseous pollutants?

NA

(vi)

Is effluent treatment plant in existence? If Yes, comment on it.

NA

(vii)

Are fume hoods of adequate design in existence and used wherever necessary?

NA

20.

RESULTS OF PREVIOUS SELF INSPECTION AND CORRECTIVE MEASURES TAKEN

Y

(i)

Is the report of previous self-inspection available?

Y

(ii)

Recommendations of previous self-inspection?

Y

(iii)

Whether corrective measure have been taken as recommended by previous self-inspection team?

Y

PARENTERAL SECTION 1.

Whether separate sections are provided for preparation of the containers and closures. Preparation of solution, Filling and Sealing Serilisation.

2.

Equipment: Whether as per shedule M Manufactring Area: i) Shortage equipment for ampoules, vials; bottles and closures. ii) Washing and drying equipment. iii) Dust proof shortage cabinet. GMP Checklist Rev 0

NA

REMARK/ COMMENTS

GMP inspection done internally once in 6 months. Last inspection done on 14.01.2008

British Standards Institution

iv) v) vi) vii) viii)

Water still. Mixing and preparation tanks or other containers. Mixing equipment where necessary Filtering equipment Hot Air Steriliser

NA

Asceptic Filling and Sealing Rooms: ix) Bacteriological filters. x) Filling and sealing unit under laminar flow work station. NA

S.NO.

CATEGORIES

COMPLIANCE Y/N/NA

General Room: xi) Inspection room xii) Leak testing equipment xiii) Labelling and packing benches xiv) Storage equipment including cold storage and refrigeration, if necessary. 3.

Whether rubber closures used are of natural or synthetic origin. Whether closures properly cleaned and sterilized (note the method). Are they tested as per ISI standards. Whether the cleaning schedule on container and closures maintained.

NA

4.

Whether the sterile containers and closures are moved to the filling area without exposure in non-sterile area. Are the following rooms with proper facilities provided before entry in to the sterile area:

NA

i) ii)

A room for removal of street clothes and shoes provided with cupboards and racks etc. A room for washing & changing into sterile overalls.

GMP Checklist Rev 0

REMARK/ COMMENTS

British Standards Institution

iii)

An airlock.

5.

Whether personnel entering in the sterile area wear clean sterile uniform. Head cover, footwear, masks and gloves Made of such material which are not likely to shed fibres (nylon, Dacron etc.)

6.

Whether movement of personnel is restricted in the sterile NA area.

7.

Whether special procedure has been established for entering and leaving the manufacturing area and sterile area. Is the procedure displayed at the entrance of the manufacturing area.

NA

NA

8.

Are the furniture provided in the section satisfactory (smooth and washable).

Y

9.

Whether sufficient UV lamps are provided in the airlock and hatches.

NA

10.

a) Is the efficacy of UV lamps monitored? (Check whether their daily burning hours are recorded and they are changed after they have burnt the specified hours.) CATEGORIES

NA

S.NO.

b) Are the UV lamps cleaned periodically?

COMPLIANCE Y/N/NA NA

11.

Whether the solution preparation room and filling and sealing rooms are air conditioned and provided with filtered air to keep positive pressure. ( State the airconditioning system-central or individual air-conditioners and the class of air cleanliness).

NA

12.

Whether ascptic handling is necessary and if so, whether central air conditioners with HEPA filters are provided.

NA

13.

Whether distillation units properly and frequently cleaned NA to eliminate contamination, pyrogenous matter, particulate matter, etc.

14.

Whether distilled water still is so designed to avoid mixup of water spra condensed water. Write the model of DW plant used. GMP Checklist Rev 0

NA

REMARK/ COMMENTS

British Standards Institution

15.

Whether fresh distilled water is used for a) Manufacturing operations (it should be within 3-4 hrs, of collection. If storing is necessary, it should be stored at 800C and above). b) Is the bulk distilled water tested for pyrogen? c) Whether adequate precautionary measures are taken to avoid contamination during collection and transfer of distilled water to the solution preparation room.

NA

16.

Whether aseptic handling is necessary. If so, whether laminar airflow system is provided in the solution filling area.

NA

17.

a) Is the plate count taken and the method used is adequate? b) Has the average number of colonies (standard limit) been determined? c) If so, is ir adequate (how it has been determined and what is the limit)? d) If the limit is higher than permissible on any day, steps taken to find out the causes etc. (check if the production is stopped.)

NA

S.NO.

CATEGORIES

18.

Are there any devices provided to note temperature of the air-conditioned area?

19.

Is the solution filtered (note the type of filter used, candles sintered, glass or membrane filter)? If the products are to be manufactured by aseptic technique, do they have filtering assembly with bacteria retaining filters. Whether the efficiency of the filters checked before operation.

20.

Whether autoclave used is adequate and is provided with an automatic device to record pressure, temperature and duration of sterlisation and whether records are GMP Checklist Rev 0

COMPLIANCE Y/N/NA Y

NA

NA

REMARK/ COMMENTS

British Standards Institution

maintained. 21.

Is the effectiveness of sterilizer checked (state the type of indicators used)?

NA

22.

What system has been established to separate products intended for sterlisation from products already sterilized?

NA

23.

Whether the dry air sterilizers and autoclaves provided have been validated for sterilization before operation and whether recoding device is provided.

NA

24.

How is the equipment sterilized if necessary?

NA

25.

Whether lot Nos are given separately for different lots of autoclave load in the same batch and are they separately tested for sterility.

NA

26.

Whether the net content of the liquid is checked.

NA

27.

Whether leak test for ampoules is performed.

NA

28.

Are the finished product visually examined for suspended NA particles. Whether visual checking unit is adequate and satisfactory.

29.

Whether adequate equipment is provided for the following operations checks and these checks are being carried-out.

NA

S.NO.

CATEGORIES

COMPLIANCE Y/N/NA NA NA NA NA NA NA NA NA NA NA

i) ii) iii) iv) v) vi) vii) viii) ix) x)

Cutting of ampoules Washing of ampoules, bottles & closures. Drying of ampoules, vials & bottles. Auto claving and sterilizing Sterilising of containers & closures. Manufacture of distilled water. Mixing, preparation & storage of solution. Filtration of solution. Filling and sealing Testing leak.

GMP Checklist Rev 0

REMARK/ COMMENTS

British Standards Institution

xi) xii)

Testing of foreign particles with black and white background. Cold storage, if necessary

NA NA

30.

Whether the equipment are designed for thorough cleaning after each batch of operation.

NA

1.

OPHTHALMIC SECTION (Drops, Solutions, Ointments, Suspensions, etc.)

NA

Equipment whether as per Schedule M i) ii) iii) iv) v) vi) 2.

3.

4.

vii) viii)

Hot air oven electrically heated with thermostatic control. Kettle, gas or electrically heated with suitable mixing. Colloid mill or ointment mill Tube filling equipment Mixing and storage tanks of stainless steel of other suitable material Sintered glass funnel seitz filter or filter candle. Liquid filling equipment Autoclaves.

Are the droppers properly cleaned and sterilized (check whether the droppers are packed in sterile cellophane packing. If supplied separately)? Is a suitable bactericidal agent added to the preparation (note the percentage of the substance added)? Are collapsible tubes cleaned with nylon brushes and high pressure air jet?

S.NO.

CATEGORIES

5.

What is the method of sterilizing collapsible tubes? If ethylene oxide is used for sterilization is residual gas removed effectively. GMP Checklist Rev 0

COMPLIANCE Y/N/NA

REMARK/ COMMENTS

British Standards Institution

6.

Is a separate area provided near the ointment section for melting, filtering and sterilization of petroleum base? (note the arrangement for directly treasferring the sterile base)

7.

Are the coarse particles of drugs made to a fine powder before incorporating into the ointment base? (Particle size should be less than 50 microns in the finished products.)

8.

Whether asceptic manipulations are carried out in a conventional sterile area or under laminar flow system.

9.

Whether sterile bulk materials and containers and closures are moved into the sterile area without exposure.

10.

Are the ointment tested for gross contaminations? (The finished products must be free from Pseudomonas aeruginosa.)

11.

Whether integrity of filters test is carried (Bubble point test) out or not in case of aseptic filling.

13.

Other remarks.

GMP Checklist Rev 0

N