annexure xix (gmp-questionnaire for packing material suppliers) merck

ANNEXURE XIX

GMP-Questionnaire for Packing Material Suppliers

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Date: 7th Oct. 2011

Supplier Name: DOCTOR PACK INDIA PRIVATE LIMITED

Address: #24 Bommasandra Jigani Industrial Estate, Bommasandra Jigani Link Road,

City: Bangalore 562106

State: Karnataka

Zip Code: 562106

Telephone (plant): +91 9591665747, +91 9686200569

(Main office): ____________________________

(Fax): __________________________

Is the company a division or subsidiary or affiliate of another corporation? No.

If yes, Name: ____________________________________

Concerned Packing material: Plastic Dropper Bottles with Nozzle and cap

Please attach a list of all products manufactured at the stated production site(s)

Is the Manufacture of the concerned products performed at different locations? No

If yes, Names: ______________________________________________________________

Addresses: ____________________________________________________________

Responsibilities/Name/Title:

Production: B . Murugan, Plant Manager

Quality Control: K.Balaji, Asst Manager

Quality Assurance: J.Sathyanarayana, Manager - Quality

If possible, please give explanations to the answers in the following questionnaire!

Please fill in the questionnaire and return it to:

Manager, Materials (Packing Material) Merck Limited

D-116, MIDC, Thane Belapur Road, Nerul, Navi-Mumbai – 400 706, India

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1. Company profile:

1.1 Size production area? 6000 Sq. Ft.

1.2 Size of warehouse? 6000 Sq. Ft

1.3 Is the site a mono production site? Yes No □

______________________________________________________________________________

1.4 Percentage of own products : 100%

1.5 Percentage of contract: ________________

1.6 Percentage of customers

Pharmaceuticals: (in %) ________________

Cosmetics: (in %) ________________

Food: (in %) ________________

Others: (in %) ________________

1.7 Personnel

Number of employee in:

Production Area 48

Quality Control 3

Research & Development NA

Quality Assurance 4

1.8 Do you perform

-Production as well as packaging? Yes No □ N.A. □

-Only production? Yes □ No □ N.A.

-Only packaging? Yes □ No □ N.A.

-Are you exclusively a trader? Yes □ No N.A. □

If you are exclusively a trader, who is the manufacturer and/or packager?

If YES:

Manufacturer: Packager:

Name ________________________________ Name _______________________________

Address _________________________________

Address_______________________________

_________________________________

_______________________________

Could we have the questionnaire completed by the manufacturer and/or packager? Yes □ No □

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1.9 Which manufacturing processes are carried out at the stated site?

Production

Yes No □ N.A. □

Processing

Yes No □ N.A. □

Printing

Yes □ No □ N.A.

Cutting

Yes □ No □ N.A.

Treatment of surface (e.g. coating, siliconization)

Yes □ No □ N.A.

Quality Control

Yes No □ N.A. □

Please briefly describe the manufacturing process: → Please enclose a flow chart (attached)

1.10 Have you been approved according to ISO (e.g. 9000 series) or by other associations?

Yes □ No □ N.A.

If YES:

Name of the associations: Already ISO 15378 System in practice and the audit will be done during Dec 2011 since the site commenced production from Jan.2011.

Date of the last audit, by: _______________________________________________________ 1.11 Are you willing to provide us with copies of your current ISO certification?

Yes □ No □ N.A.

Latest date of certification: ______________________________________________________

1.12 Would you agree to on-site audit? Yes No □

1.13 Are you willing to inform us prior to the implementation of major changes in

-The location of production? Yes No □ N.A. □

-Equipment of production? Yes No □ N.A. □ -The manufacturing methods? Yes No □ N.A. □

-The technology? Yes No □ N.A. □

-The quality specification? Yes No □ N.A. □

-The test methods? Yes No □ N.A. □

-The answer to the questionnaire? Yes No □ N.A. □

2. Storage and handling of key raw materials incoming and final goods:

2.1 Are raw materials and incoming goods stored separated from production areas?

Yes No □ N.A. □

A dedicated place assigned for each raw material and Packing material

2.2 Do you have a suitably equipped area for -Incoming goods? Yes No □ N.A. □

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-Key raw materials? Yes No □ N.A. □

-Semi finished products? Yes □ No □ N.A.

-Finished products? Yes No □ N.A. □

-Packaging materials? Yes No □ N.A. □

-Rejected materials? Yes No □ N.A. □

-Sampling? Yes No □ N.A. □

_____________________________________________________________________________

2.3 Are there separated quarantine areas for materials awaiting final testing?

Yes No □ N.A. □

Quarentine areas are marked with yellow border line.

2.4 Are there separated quarantine area for rejected, returned or recalled materials? Yes No □ N.A. □

____________________________________________________________________

2.5 Do you apply the “First in first out” or “First expiry first out” principle? Yes No □ N.A □

_______________________________________________________________________________

2.6 Do labels indicate the name or identifying code, batch number and storage conditions if

appropriate?

Yes No □ N.A. □

___________________________________________________________________

Are supplier certificates of analysis for all raw materials available?

Yes No □ N.A. □

2.7 Are incoming materials checked prior to their use, or is there assurance e.g. by certificates of

analysis that these materials conform with their specifications? Yes No □ N.A. □

___________________________________________________________________________

2.8 Is accepted material properly labeled or otherwise identified? Yes No □ N.A. □

___________________________________________________________________________

2.9 Are written procedures in place describing the receipt, identification, quarantine, sampling,

examination, testing and release of incoming material? Yes No □ N.A. □

___________________________________________________________________________

2.10 Is access to warehouse restricted to authorised personnel? Yes No □ N.A. □

___________________________________________________________________________

2.11 Are written procedures used to verify storage requirements? Yes No □ N.A. □

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___________________________________________________________________________

2.12 Do you systematically control according to written instructions for sensitive products?

-The temperature? Yes □ No □ N.A.

-Humidity of the warehouse? Yes □ No □ N.A.

-Do you maintain the relevant records? Yes □ No □ N.A.

___________________________________________________________________________

2.13 Do you perform documented PEST – CONTROL in your warehouse? Yes No □ N.A. □

2.14 Distribution procedures

Can you ensure that the contract acceptor for transportation knows and follows the

appropriate transport and storage conditions for the material? Yes No □ N.A. □

___________________________________________________________________________

2.15 Do you have a system in place by which the distribution of each batch of material can be

readily determined to permit the recall? Yes No □ N.A. □

Batch Traceability effectively done with bar coding system. It can be traced out from finished goods to the raw material vise versa. (SOP: DPI-QA-SP008)

3. Production:

3.1 Buildings and facilities

3.1.1 Do building and facilities have adequate space for the orderly placements of equipment’s and

materials to prevent mix up? Yes No □ N.A. □

All machines and equipments are in order materials are labeled and controlled by the Quality department, material movement sop in place for regular operation of materials start from Stores to the production.

3.1.2 Are there written cleaning instructions and records? Yes No □ N.A. □

Cleaning done before line startup and line clearance approval has been given by the Quality Department.

3.1.3 Particles of broken glass in production units are dangerous. Therefore in may companies

glass policies are defined. Does a glass policy exist? Yes No □ N.A. □

In Clean room area No glassware or glass equipments are used. Light fixtures are covered with Acrylic sheet. However, glass policy is in place.

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3.1.4 Is there an existing hygiene monitoring program defined for the production area? Yes No □ N.A. □

SOP in place.(SOP: DPI-QA-SP006)

3.1.4.1 Are there written procedures for

-Building sanitation? Yes No □ N.A. □

-Cleaning? Yes No □ N.A. □

-Pest control? Yes No □ N.A. □

___________________________________________________________________________

3.2 Equipment

3.2.1 Equipment and utensils should be cleaned, stored, and where appropriate sanitized or

sterilized to prevent carry-over of material which would alter the quality of the packing

material beyond the official or other established specifications. Non-dedicated equipment should be cleaned between productions of different materials to prevent cross-contamination.

Acceptance criteria for residues and the choice of cleaning procedures and cleaning agents should be defined and justified if applicable.

3.2.1.1 Are materials produced with dedicated equipment? Yes □ No □ N.A.

Injection Blow Moulding – for Bottle Injection Moulding - for Nozzle and Cap

3.2.1.2 If no, which products are produced using the same equipment as the concerned products on Page 1?

All the machines & Moulds are validated to the many products on the same machine.

3.2.2 Schedules and procedures (including assignment of responsibility) should be established for

the preventive maintenance of equipment. Control, weighing, measuring, monitoring and testing equipment should be calibrated

according to written procedures and an established schedule. Equipment calibration should be performed using standards traceable to certified standards, if they exist.

Records of these calibrations should be maintained.

Are there written -Maintenance instructions and records Yes No □ N.A. □

-Cleaning instructions and records Yes No □ N.A. □

-Operating instructions and records Yes No □ N.A. □

-Calibration instructions and records Yes No □ N.A. □

Available for the equipment and utilities? Yes __________________________________________________________________________

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3.2.3 Before initiating process validation activities, appropriate qualification of critical equipment

and ancillary system should be completed. 3.2.3.1 Do you apply the HACCP concept? Yes No □ N.A. □

___________________________________________________________________________

3.2.3.2 Do you define in-process controls after performing a risk analysis? Yes No □ N.A. □

___________________________________________________________________________

___________________________________________________________________________

3.2.3.3 Are the production equipment/utilities qualified with regards to

-Design Qualification Yes No □ N.A. □

-Installation Qualification Yes No □ N.A. □

-Operational Qualification Yes No □ N.A. □

-Performance Qualification Yes No □ N.A. □

___________________________________________________________________________

3.2.3.4 Are the production equipment/utilities qualified

Prospectively? Yes No □ N.A. □

Retrospectively? Yes □ No □ N.A.

All equipments & machines are commissioned on Jan 2011.

3.2.4 Are your instruments (e.g. balance, measuring instruments) registered? Yes No □ N.A. □

___________________________________________________________________________

3.2.5 Adequate ventilation, air filtration and exhaust systems should be provided, where

appropriate. These systems should be designed and constructed to minimize risks of cross contamination and should include equipment for control of air pressure, micro organisms (if

appropriate), dust, humidity and temperature.

3.2.5.1 Is there any air-handling system

-In the manufacturing rooms? Yes No □ N.A. □

-In the packaging rooms? Yes No □ N.A. □

(Describe briefly your air-handling system, e.g. laminar flow, Clean Room Class) Validated Clean Room Class 8(ISO), Area 5000 Sq,Ft. having 27 HEPA filters of 0.3 micron size of 30 cycles air change per hour maintained temperature 72F RH -45-55% includes for RM preparation area. Support service room for FP preparation all under classified air handling area.

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3.2.5.2 Are there equipment log books available? Yes No □ N.A. □

___________________________________________________________________________

3.2.6 Have you installed automatic inspection equipment (e.g. opto-electronic system, camera inspection systems or barcode-readers)? Yes No □ N.A. □

→ If yes, please answer the following questions:

Have you implemented a 100% monitoring systems? Yes No □ N.A. □

Do you regularly challenge the systems to verify the continued functionality, reliability and good working condition? Yes No □ N.A. □

Is a specification/description for the functionality existing? Yes No □ N.A. □

Bar coding system is in practice for Finished Goods. 3.3 Manufacturing / Packaging

3.3.1 Is the product manufactured -continuously Yes □ No N.A. □

-batch wise Yes No □ N.A. □

Please explain your method of issuing batch numbers:

Each work Order will have separate batch number and quantity based on the work order.

How do you define a homogeneous batch?

Homogeneous batch of a product that complies within the specification limits that is being

ensured on hourly check on visual, once in four hours check by functional check, and final

inspection as per the Test Matrix.

Is the homogeneity of the batches validated and documented? Yes. All Products are validated on all the machines and IQ,OQ,PQ of the each product is available.

3.3.2 At which stage do you perform the full batch analysis -At each sub batch stage Yes □ No

-At the final batch size stage Yes No □

Please describe briefly your quality control steps including test parameters as well as the

frequency of the testing.

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After start up of the machine, line clearance will be approved by Quality then BMR is

generated with the first full shot product is being tested for complete analysis. After the

approval of the startup product , control sample will be prepared, attached with the BMR and

then the machine is allowed to run continuously.

In process check will be done visually every hour by the operator, online QC check done

once in four hours for visual, functionality test for full shot and critical dimension checks

once per day.(Sampling rate 10%) as per the Test Matrix (attached).

A one set of control sample will be collected in the middle of the batch. A composite sample

will be collected at the end of the batch and attached with the BMR.

3.3.3 Please describe your sampling procedure for the finished product.

n+1 sampling applicable to Finished product.

3.3.4 Critical weighing, measuring, or subdividing operations should be witnessed or subjected to an equivalent control. Actual yields should be compared with expected yields. Any deviation

should be documented and explained. Any critical should be investigated.

Are approved written procedures available for each step of -Manufacturing? Yes No □ N.A. □

-Packaging? Yes No □ N.A. □

describing all critical steps.

3.3.5 Materials to be reprocessed or reworked should be appropriately controlled to prevent unauthorized use.

Does the written procedure cover Reprocessing? Yes □ No □ N.A

Reworking? Yes No □ N.A. □

No reprocess work being done in the manufacturing. All online rejection will be discarded as waste. Reworking done for the product mix up in final stage, defective products will be segregated and packed. Before the pack, Quality inspections are done, verified and approved by Quality.

3.3.6 Critical in-process controls should be stated in writing and approved by the quality units.

Written procedures should describe the sampling methods for in-process materials.

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Are there adequate in-process procedures performed? Yes No □ N.A. □

___________________________________________________________________________

3.3.6.1 Is the in-process control supervised by the QA or QC organization? Yes No □ N.A. □

___________________________________________________

3.3.6.2 Procedures should be established to reconcile the quantities of labels issued, used, returned

and to evaluate discrepancies found between the number of containers labeled and the

number of labels issued. All excess labels bearing batch number or other batch-related printing like order no. /consignment no. should be destroyed.

3.3.6.2.1 Do you have a system for reconciliation of labels? Yes No □ N.A. □

___________________________________________________ 3.3.6.3 Are process waste and unusable residues destroyed? Yes No □ N.A. □

If no, do you reprocess the waste and unusable residues? 3.3.6.4 Do you release the printers copy? → If yes, do you use an unchangeable reference standard?

Yes □ No N.A. □

3.3.6.5 Do you check double sheet feeling during printing? Yes □ No N.A. □

3.3.6.6 In case of digital printing, please answer the following questions:

Do you check correct transfer of the master artwork file from the customer? Yes □ No □ N.A.

Do you prevent unintentional use of incorrect artwork files? Yes □ No □ N.A.

Do you ensure that no obsolete artwork files can be used? Yes □ No □ N.A.

Do you modify customer artwork files (e.g. EPS files)? Yes □ No □ N.A.

If yes, how do you validate this procedure? Yes □ No □ N.A.

Do you handle protected pdf-files? Yes □ No □ N.A.

Do you use an electronic text control system? Yes □ No □ N.A.

Do you use a CTP printing? Yes □ No □ N.A.

3.3.6.7 In case of production of reel-fed materials, please answer the following questions:

Is the batch identity, reel number and production date recorded on the inner face of the core

for each individual reel? Yes □ No □ N.A.

Are splices marked using a brightly colored adhesive tape on both sides of the web?

Yes □ No □ N.A.

3.3.6.8 Do you use different uses per artwork pages?

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→ If yes, how do you track and document this?

__________________________________________________________________________________

3.4 Shipping

3.4.1 Packing materials should be transported in a manner that does not adversely affect their quality.

3.4.1.1 Are written procedures used to verify shipping requirements? Yes No □ N.A. □

____________________________________________________

3.4.1.2 Does your contractor for transportation know and follow the appropriate transport and storage conditions?

Yes No □ N.A. □

___________________________________________________ 3.4.2 Is documentation enclosed in each shipment?

Yes No □ N.A. □

___________________________________________________________________________

Which documentation? Delivery Chalan, CoA, Invoice(if required), transport documents (excise, etc.,)

3.4.3 Do you keep records of delivery?

-By customers? Yes No □ N.A. □

-By batch numbers? Yes No □ N.A. □

___________________________________________________

3.4.4 How is the identity of each shipping container guaranteed?

A check list is recorded for each dispatch based on the reference from the work order. As per the work order the bar-coding label and shipper labels are prepared and pasted on each bag(during production)/carton. After the Quality verification the shipper label will be pasted over the carton before dispatch.

3.4.5 Do the parameters listed below appear on every packaging unit?

-Name of the supplier Yes No □ N.A. □

-Name and batch no. of the product Yes No □ N.A. □

-Quantity per unit Yes No □ N.A. □

___________________________________________

Are you willing to provide other information requested by us?

Yes No □ N.A. □

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3.4.6 Please give the mode of labeling for the products sent to us:

-labels (cut or roll) Yes No □ N.A. □

-painted on Yes □ No N.A. □

-Other Yes □ No N.A. □

___________________________________________________________________________

3.5 Validation

Validation policy should exist and persons responsible for design, review, approval and documentation should be documented. The critical parameters/attributes should be identified

and the necessary ranges should be defined for the reproducible operation.

3.5.1 Is validation performed

-For manufacturing methods? Yes No □ N.A. □

- For computerized system? Yes □ No □ N.A.

___________________________________________________________________________

3.5.2 Does validation documentation cover a written validation protocol specifying critical process

steps and acceptance criteria? Yes No □ N.A. □

___________________________________________________________________________

3.5.3 Does validation documentation cover validation report summarizing the results, deviations

and drawing the appropriate conclusion? Yes No □ N.A. □

_________________________________________________________________________

3.6 Personnel

3.6.1 There should be an adequate number of personnel qualified by appropriate education,

training and/or experience to perform and supervise the manufacturing operations.

Training should be regularly conducted by qualified individuals and should cover at a

minimum the particular operations that the employees perform and GMP. Personnel should perform good sanitation and health practice.

Personnel should wear clean clothing suitable for the manufacturing activity. Additional protective apparel, such as head, face, hand, and arm coverings, should be worn, when

necessary to protect the products from contamination. Smoking, eating, drinking, chewing and the storage of food should be restricted to certain

designated areas separate from the manufacturing areas.

Are there detailed hygiene programs established and adapted to the different needs within

the factory? Yes No □ N.A. □

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Clean room entry exit procedure in place DPI-QA-SP007

3.6.2 Are all employees in the manufacturing process given periodic medical check-ups? Yes No □ N.A. □

_________________________________________________________________________

3.6.3 Is it ensured that no person with an infectious disease will come into contact with the products?

Yes No □ N.A. □

_________________________________________________________________________

3.6.4 Is there a prohibition for eating, drinking, chewing and smoking in any area where the

product might be adversely affected? Yes No □ N.A. □

_________________________________________________________________________

3.6.5 Are there garment instructions? Yes No □ N.A. □

__________________________________________________________________________

3.6.6 Are there adequate washing and toilet facilities provided for personnel? Yes No □ N.A. □

___________________________________________________________________________

3.6.7 Are these facilities separated from the manufacturing areas? Yes No □ N.A. □

___________________________________________________________________________

4 Batch – Documentation, Specifications

4.1 The issuance, revision, superseding and withdrawal of all documents should be controlled by

maintaining the revision histories. All production, control, and distribution records should be retained. Corrections to entries should be

dated and signed and leave the original entry still legible.

Batch production records should include complete information relating the production and control of each batch. They should be checked before issuance to ensure that it is the correct version and a

legible accurate reproduction of the master production instruction. The batch production record should include a reference to the current master production being used.

4.1.1 Are batch record properly assembled (including reprocessing)? Yes No □ N.A. □

Reprocessing Not Applicable to our process.

4.1.2 Do you keep batch records? Yes No □ N.A. □

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How long do you keep batch records: 3 +2 Yrs 4.2 Are deviations, incidents and rework of batches

-Investigated? Yes No □ N.A. □

-Evaluated? Yes No □ N.A. □

-Reviewed? Yes No □ N.A. □ -Approved? Yes No □ N.A. □

by Quality Unit (QC/QA)?

SOP attached (DPI-QA-SP003)

6. Quality Control:

6.1 Is the Quality Control Department independent from production? Yes No □ N.A. □

_________________________________________________________________________________

6.1.1 Are all test performed in-house Yes No □ N.A. □

_________________________________________________________________________________

6.1.2 If not who is performing the tests and which parameters?

__________________________________________________________________________________ ____________________________________________________________________

6.2 Are there written

-qualification instructions and records Yes No □ N.A. □

-calibration instructions and records Yes No □ N.A. □

-maintenance instructions and records Yes No □ N.A. □

available for the laboratory instruments?

__________________________________________________________________________________

6.3 Do you have quality specifications for your

Raw materials? Yes No □ N.A. □

Products? Yes No □ N.A. □

_________________________________________________________________________________

6.4 Are the tests performed according to approved written test procedures? Yes No □ N.A. □

_________________________________________________________________________________

6.5 Are written procedures available for the staff in the QC labs? (specifications, test procedures, SOPs) Yes No □ N.A. □

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_________________________________________________________________________________

6.6 Are all tests mentioned on the Certificate of Analysis performed for each batch? Yes No □ N.A. □

_________________________________________________________________________________

6.7 Are written procedures for sampling available? Yes No □ N.A. □

_________________________________________________________________________________

6.8 Are retention samples taken? Yes No □ N.A. □

_________________________________________________________________________________

6.9 Retention samples of each batch should be retained one year after the expiry date of the batch.

Sufficient quantities should be retained to conduct at least two full specification analyses.

Are the retention samples stored under defined conditions? Yes No □ N.A. □

Retention period for samples : Raw material – 1 year For Finished goods 3 +2 Yrs.

6.10 Who is responsible for the batch release? (Department and function)

QA Manager /Asst. Manager (Quality)

________________________________________________________________________________

7. Quality Assurance

7.1 Who is the person in charge of the Quality Assurance?

Name: J.Sathyanarayana

7.2 Is the Quality Assurance Department independent from production? Yes No □ N.A. □

_____________________________________________QA Manager reports to MD

7.3 Is there a training procedure for all employees in place? Yes No □ N.A □

_________________________________________________________________________________

Please give a brief description: Induction Training programme at the time of Joining. On job training for each employees, cGMP, Personal Hygiene & Clean room entry exit procedure for

Production,Stores,Quality Dept. Assessment after training in place. __________________________________________________________________________________

__________________________________________________________________________________

7.4 Have you got a system of self-inspection/audit?

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Yes No □ N.A. □

Please give a brief description:

We have qualified internal auditor, internal audit is done once per six month, SIP will be done by the Quality Manager once per month. The observations are discussed in the meeting with all Dept. Heads and action plan will be circulated. Each task completion will be verified and closed by the Quality Manager.

7.5 Have you got a system for supplier qualification? Yes No □ N.A. □

Please give a brief description:

Packaging material suppliers manufacturing sites are visited by the Quality department to verify and evaluate the cGMP and storage condition of the supplier with a questionnaire and subsequent approval. Majority of Raw materials are imported from France/German/Italy from a monopoly manufacturer of PE called Leyondell Bassel – their materials are 21 CFR compliance.

7.6 Are all essential processes of quality assurance regulated in the form of written procedures? Yes No □ N.A. □

Frequency of supervision: once/yr (Question Not clear)

__________________________________________________________________________________

7.7 Are corrective actions taken and supervised? Yes No □ N.A. □

_________________________________________________________________________________

7.8 Do you routinely inform you customer about changes in the production process? Yes No □ N.A. □

Do you routinely inform your customer about changes in the production site? Yes No □ N.A. □

Do you routinely inform your customer about changes in the product specification? Yes No □ N.A. □

_________________________________________________________________________________

7.9 Have you got written procedures and records for

-complaints Yes No □ N.A. □

-recalls Yes No □ N.A. □

-product failures Yes No □ N.A. □

-change Control Yes No □ N.A. □

-Out of Specification results Yes No □ N.A. □

in place ?

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All Sop’s and Formats are in place. Since it is new company No complaints, recalls, failures, change control occurred.

annexure xix (gmp-questionnaire for packing material suppliers) merck

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