ANNEXURE XIX

GMP-Questionnaire for Packing Material Suppliers

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? 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 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

Page 1 of 17

ANNEXURE XIX

GMP-Questionnaire for Packing Material Suppliers

1. 1.1 1.2 1.3 1.4 1.5 1.6 Company profile: Size production area? Size of warehouse? Is the site a mono production site? Percentage of own products : Percentage of contract: Percentage of customers Pharmaceuticals: (in %) Cosmetics: (in %) Food: (in %) Others: (in %) 1.7 Personnel Number of employee in: Production Area Quality Control Research & Development Quality Assurance 1.8 Do you perform -Production as well as packaging? -Only production? -Only packaging? -Are you exclusively a trader? Yes Yes Yes Yes No No No No N.A. N.A. N.A. N.A. 48 3 NA 4 ________________ ________________ ________________ ________________ 100% ________________ 6000 Sq. Ft. 6000 Sq. Ft Yes No

______________________________________________________________________________

If you are exclusively a trader, who is the manufacturer and/or packager? If YES: Manufacturer: Name Packager: ________________________________ Name _______________________________ Address_______________________________ _________________________________ _______________________________ Could we have the questionnaire completed by the manufacturer and/or packager? Yes Page 2 of 17 No

Address _________________________________

ANNEXURE XIX

GMP-Questionnaire for Packing Material Suppliers

1.9 Which manufacturing processes are carried out at the stated site? Production Processing Printing Cutting Treatment of surface (e.g. coating, siliconization) Quality Control Yes Yes Yes Yes Yes Yes No No No No No No N.A. N.A. N.A. N.A. N.A. N.A.

Please briefly describe the manufacturing process: Please enclose a flow chart (attached) 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. 1.11 Date of the last audit, by: _______________________________________________________ Are you willing to provide us with copies of your current ISO certification? Latest date of certification: 1.12 1.13 Yes No N.A. ______________________________________________________ Yes Yes Yes Yes Yes Yes Yes Yes No No No No No No No No N.A. N.A. N.A. N.A. N.A. N.A. N.A.

1.10

Would you agree to on-site audit? -The location of production? -Equipment of production? -The manufacturing methods? -The technology? -The quality specification? -The test methods? -The answer to the questionnaire?

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

2. 2.1

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

Page 3 of 17

ANNEXURE XIX

GMP-Questionnaire for Packing Material Suppliers

-Key raw materials? -Semi finished products? -Finished products? -Packaging materials? -Rejected materials? -Sampling? 2.3 Yes Yes Yes Yes Yes Yes No No No No No No N.A. N.A. N.A. N.A. N.A. N.A.

_____________________________________________________________________________ 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 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 2.7 No N.A. 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. ___________________________________________________________________________ Is accepted material properly labeled or otherwise identified? Yes No N.A. ___________________________________________________________________________ Are written procedures in place describing the receipt, identification, quarantine, sampling, examination, testing and release of incoming material? Yes No N.A. ___________________________________________________________________________ Is access to warehouse restricted to authorised personnel? Yes No N.A. ___________________________________________________________________________ Are written procedures used to verify storage requirements? Yes Page 4 of 17 No N.A.

_______________________________________________________________________________ 2.6

2.8

2.9

2.10

2.11

ANNEXURE XIX

GMP-Questionnaire for Packing Material Suppliers

___________________________________________________________________________ 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 2.14 Do you perform documented PEST CONTROL in your warehouse? Yes 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. 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. 3.1 3.1.1 Production: Buildings and facilities Do building and facilities have adequate space for the orderly placements of equipments and materials to prevent mix up? Yes No N.A.

3.1.2

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.
Are there written cleaning instructions and records? Yes

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.

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.

Page 5 of 17

ANNEXURE XIX

GMP-Questionnaire for Packing Material Suppliers

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 3.2.1 Equipment 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

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

No

N.A.

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 -Cleaning instructions and records -Operating instructions and records -Calibration instructions and records

Yes Yes Yes Yes

No No No No

N.A. N.A. N.A. N.A.

Available for the equipment and utilities? Yes __________________________________________________________________________

Page 6 of 17

ANNEXURE XIX

GMP-Questionnaire for Packing Material Suppliers

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 -Installation Qualification -Operational Qualification -Performance Qualification Yes Yes Yes Yes No No No No N.A. N.A. N.A. N.A.

___________________________________________________________________________ 3.2.3.4 Are the production equipment/utilities qualified Prospectively? Retrospectively? Yes Yes No No N.A. 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. ___________________________________________________________________________ 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

3.2.5.1 Is there any air-handling system -In the manufacturing rooms? -In the packaging rooms? Yes Yes No No N.A. 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.

Page 7 of 17

ANNEXURE XIX

GMP-Questionnaire for Packing Material Suppliers

3.2.5.2 Are there equipment log books available?

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

3.2.6

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 3.3.1 Manufacturing / Packaging Is the product manufactured -continuously Yes -batch wise Yes Please explain your method of issuing batch numbers: How do you define a homogeneous batch? No No N.A. N.A.

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

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 -At the final batch size stage Yes

No No

Please describe briefly your quality control steps including test parameters as well as the frequency of the testing.

Page 8 of 17

ANNEXURE XIX

GMP-Questionnaire for Packing Material Suppliers

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 3.3.4 Please describe your sampling procedure for the finished product.

n+1 sampling applicable to Finished product.

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? -Packaging? describing all critical steps. Yes Yes No No N.A. N.A.

3.3.5

Materials to be reprocessed or reworked should be appropriately controlled to prevent unauthorized use. Does the written procedure cover Reprocessing? Reworking? Yes Yes No No N.A 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.

Page 9 of 17

ANNEXURE XIX

GMP-Questionnaire for Packing Material Suppliers

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 ___________________________________________________ No N.A. N.A.

3.3.6.3 Are process waste and unusable residues destroyed? Yes 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 Do you prevent unintentional use of incorrect artwork files? Yes No Do you ensure that no obsolete artwork files can be used? Yes No Do you modify customer artwork files (e.g. EPS files)? Yes No If yes, how do you validate this procedure? Yes No Do you handle protected pdf-files? Yes No Do you use an electronic text control system? Yes No Do you use a CTP printing? Yes No N.A. N.A. N.A. N.A. N.A. N.A. N.A. 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 3.3.6.8 Do you use different uses per artwork pages? N.A.

Page 10 of 17

ANNEXURE XIX

GMP-Questionnaire for Packing Material Suppliers

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.,) Do you keep records of delivery? -By customers? Yes No -By batch numbers? Yes No ___________________________________________________ 3.4.4 How is the identity of each shipping container guaranteed? N.A. N.A.

3.4.3

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.
Do the parameters listed below appear on every packaging unit? -Name of the supplier Yes -Name and batch no. of the product Yes -Quantity per unit Yes ___________________________________________ Are you willing to provide other information requested by us? Yes Page 11 of 17 No N.A. No No No N.A. N.A. N.A.

3.4.5

ANNEXURE XIX

GMP-Questionnaire for Packing Material Suppliers

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. ___________________________________________________________________________ Does validation documentation cover a written validation protocol specifying critical process steps and acceptance criteria? Yes No N.A. ___________________________________________________________________________ Does validation documentation cover validation report summarizing the results, deviations and drawing the appropriate conclusion? Yes No N.A. _________________________________________________________________________ Personnel 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. Page 12 of 17

3.5.2

3.5.3

3.6 3.6.1

ANNEXURE XIX

GMP-Questionnaire for Packing Material Suppliers

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. _________________________________________________________________________ Is it ensured that no person with an infectious disease will come into contact with the products? Yes No N.A. _________________________________________________________________________ Is there a prohibition for eating, drinking, chewing and smoking in any area where the product might be adversely affected? Yes No N.A. _________________________________________________________________________ Are there garment instructions? Yes

3.6.3

3.6.4

3.6.5

No

N.A.

__________________________________________________________________________ 3.6.6 Are there adequate washing and toilet facilities provided for personnel? Yes No N.A. ___________________________________________________________________________ Are these facilities separated from the manufacturing areas? Yes No N.A. ___________________________________________________________________________ Batch Documentation, Specifications 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. No N.A.

3.6.7

4 4.1

4.1.1

Are batch record properly assembled (including reprocessing)? Yes Reprocessing Not Applicable to our process. 4.1.2 Do you keep batch records? Yes

No

N.A.

Page 13 of 17

ANNEXURE XIX

GMP-Questionnaire for Packing Material Suppliers

How long do you keep batch records:

3 +2 Yrs

4.2 Are deviations, incidents and rework of batches -Investigated? -Evaluated? -Reviewed? -Approved? by Quality Unit (QC/QA)? Yes Yes Yes Yes No No No No N.A. N.A. N.A. N.A.

SOP attached (DPI-QA-SP003)

6. 6.1 6.1.1 Quality Control: Is the Quality Control Department independent from production? Yes No N.A. _________________________________________________________________________________ Are all test performed in-house Yes No N.A. _________________________________________________________________________________ If not who is performing the tests and which parameters? __________________________________________________________________________________ ____________________________________________________________________ 6.2 Are there written -qualification instructions and records -calibration instructions and records -maintenance instructions and records Yes Yes Yes No No No N.A. N.A. N.A.

6.1.2

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

6.5

Page 14 of 17

ANNEXURE XIX

GMP-Questionnaire for Packing Material Suppliers

_________________________________________________________________________________ 6.6 6.7 Are all tests mentioned on the Certificate of Analysis performed for each batch? Yes No N.A. _________________________________________________________________________________ Are written procedures for sampling available? Yes No N.A. _________________________________________________________________________________ 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 Retention period for samples : 6.10 No N.A.

6.8

Raw material 1 year For Finished goods 3 +2 Yrs.

Who is responsible for the batch release? (Department and function) QA Manager /Asst. Manager (Quality) ________________________________________________________________________________

7. 7.1

Quality Assurance 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 Is there a training procedure for all employees in place? Yes No N.A _________________________________________________________________________________

7.3

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? Page 15 of 17

ANNEXURE XIX

GMP-Questionnaire for Packing Material Suppliers

Yes Please give a brief description: No N.A.

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 Please give a brief description: No N.A.

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. _________________________________________________________________________________ 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.

7.8

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 -recalls -product failures -change Control -Out of Specification results in place ? Yes Yes Yes Yes Yes No No No No No N.A. N.A. N.A. N.A. N.A.

Page 16 of 17

ANNEXURE XIX

GMP-Questionnaire for Packing Material Suppliers

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

Page 17 of 17