Report on Nuvista Pharma Ltd (Part-13)

QUALITY CONTROL

Quality control is that part of GMP which is concerned with sampling specification and testing and with organization documentation and release procedures which ensures that the necessary and relevant tests are infact carried out and that materials are not released for sale or supply untill this quality has been judged to be satisfactory.

Activities of the Quality Control Department:

1.         Receiving of the samples to be tested from QA department.
2.         Issuing release, reject or quarantine advice for each batch of raw material and final product.
3.         Assessment of the intermediate products & bulk products for further            
            processing.
4.         Performing all tests procedure for all incoming samples according to the        schedule.
5.         Maintaining batch wise full quality control tests records & signature of the 

            Person(s) who perform the test.
6.         Performing environmental monitoring tests.
7.         Calibrations and standardization of laboratory equipment’s.
8.         Ensuring precision and accuracy of all testing methods.
9.         Control of all laboratory reagents.
10.       Research & development of any new method & its validation.
11.       Testing of any return goods.
12.       Stability tests for finished products
Working Division of Quality Control Department:
Quality control (QC) department can be further divided into four corresponding sections:

ü  Microbiological section.

ü   Packaging section.

ü  Finished product.

ü  Raw Material.

Lab Facility: Lab facility of Nuvista Pharma Limited is so excellent. Their lab can be described in the following way.
1. Analytical lab

2. Instrumental lab

3. Microbiological lab

Quality control department serves the following functions-

1. Before purchasing of raw materials QC department test the all B.P.& U.S.P specifications of raw materials from the sending sample
2. When raw materials are sent by the source in terms of invoice Q.C. department collects the sample on the basis  invoice & labeled an under test sticker.
3. If it meets all E.P., U.S.P., B.P. specification then a passed sticker is labeled.
4. After manufacturing of pharmaceutical preparation Q.C department collects sample from bulk product & test its physical & chemical parameters
5. Q.C department also tests the packaging materials & inspects its printing name corresponding to the product.

6. Q.C department tries to recover tests the quality after final packaging.
7. If any finished product is damaged during transfer to CWH Q.C department try to recover the product as a return goods.
8. After market complain Q.C department tests the product whether the complain is justified or not in respect to the keeping sample
9. Any new products or raw materials supplied by the source is tested by the Q.C respectively for 3 batches' & set its clear information for monitoring or keeping studies
10. The Q.C department tests water that is used for manufacturing process as it meets its specification.

Quality control department does following tests:

           ª For Raw Materials:

                            Physical test:

v    Appearance

v    Identity

ü  IR

ü  Melting point

ü  HPLC.

v    Clarity of solution.

v    Color of solution.

v    P^H (Acidity/Alkalinity).

v    Specific optical rotation.

v    Refractive index.

v    Viscosity.

v    Bulk density.

v    Sieve test.

v    Assay.

v    Loss on drying or moisture or water content.

v    Total impurities.

v    Related substances (HPLC).

Chemical test: potency.

          ªFor Bulk product:

                              A. Solid

                                         Physical test:

                                                  1.Dissolution test

                                                  2. Disintegration test

                                                  3. Uniformity weight

                                                 4. Average weight

                                                  5. Hardness

                                                  6. Thickness

                                                7. Friability

                             B. Liquid:

   Physical test:

                                                       1. Appearance

                                                       2. Weight per ml

                                                       3. Refractive index

                                                       4. Viscosity

                                                       5. Color

                 Chemical Test:                           Active ingredient

                                Potency

                    

                                                                                             Preservative

                            C. Dry Granulation Powder:

                Physical test:

                                      1. Appearance of dry granules.

                                      2. pH of prepare syrup.

                                      3. Water content.

                                      4. Reconstitution time.

                                      5. Seive test.

                                      6. Inspection of test syrup.

                                      7. Appearances of prepare syrup.

                                           Chemical test:    Potency.

             D. Semisolid:

                          Physical test:

                                      1. Apparaence

                                      2. PH   

                                      3. Particle size

                                      4. Water content.

                                            Chemical test: Potency.

 ª For packaging Material

The following tests of the packaging material are performed in QC department:
Items                                                       Tests          
Carton                              Appearance, weight, moisture content.       
Shipping carton                Weight, dimension, thickness, appearance             
In Process Control (IPC):

IPC test are designed to ensure that the process is under control throughout the manufacturing to have the right things happens at every stage to make a successful batch at the first attempt. The full benefits of IPC come from getting the things’Right the First Time’

. Major advantage of IPC:

¨       Allows timely action.

¨       Improves productivity.

¨       Reduces rejection cost.

¨       Reduces batch testing at the end.

¨       Reduces the chance of batch failure.

Stability Testing: The quality control department of Nuvista Pharma Limited also performs stability testing for both the marketed product and the development products.

Report on Nuvista Pharma Ltd (Part-12)

QUALITY CONTROL DEPARTMENT of Nuvista Pharma Ltd

Quality Operation Department is very important for a pharmaceutical industry to maintain GMP. The concept of total quality management and total quality control refers to the process of striving to produce a perfect product by a series of measures requiring an organized effort by the entire company to prevent or eliminate errors at every stage in production.

Although the responsibility for assuring product quality belongs principally to QOD, it involves many departments and disciplines within the company. To be effective it must be supported by a team effort.

The QOD is vital for a pharmaceutical industry since it controls and assures for quality of the products starting from the raw materials to the finished product till the customers consume it. All kinds of necessary steps are taken by this department to serve a quality product to the end users.

Equipment or instruments used for Quality Operation:

• Hardness Tester, Model: B 24, Western Germany.
• Friability Tester, Model: T A Fed. Rep. Germany.
• Vaccum Oven
• UV
• Dissolution Tester
• Disintegration Tester
• Ultrasonic Bath
• Viscometer   
• Karl-Fischer Titrator
• Analytical Balance.
• Centrifuger
• High Performance Liquid Chromatography (HPLC)

Quality Assurance

In addition to day to day production also matter day to day. It concerns original design and development product distribution, dispensing upto the administration to the patients Nuvista Pharma Limited gives priority to produce quality product. They believe that only quantity product can satisfy the consumer and a satisfied customer is a great advertiser for the company. For this reason they have taken a stick and inflexible process to check the product for erosion of any kind of defects. For Quality control Nuvista procures Quality raw Materials from their approved source.

Types of work of QA:

1)      Raw materials analysis

Ø     Source development

Ø     Commercial Consignment

Ø     Re-testing

Ø     Keeping sample & relevant documentation

2)      Packaging material analysis

Ø    Source development

Ø    Commercial Consignment

3)    Finish product analysis

Ø    In process

Ø    Bulk product

4)   Water analysis

5)   Calibration

6)      Validation

7)      Packed Product analysis

8)      In Process

9)      Packet product

10)  Stability study

11)  Product monitoring

12)  Environmental monitoring

13)  Dust monitoring

14)  Documentation

Flow Chart of Releasing Finished Product:

Report on Nuvista Pharma Ltd (Part-11)

PARENTERAL DEPARTMENT

Injections are sterile and pyrogen free products that intended to be administrated in the body with the help of syringe or needles through various route such as IV, IM etc. As the products directly go to the circulation, they must be free from any microbial contamination, toxic compound that should process & exceptionally high level of purity.

Nuvista Pharma has separate section for injections which consists several subunits-

• Aseptic room for filling and sealing
• Sterilization room (autoclaving and terminal sterilization)

Facility status for aseptic area:

• Room temperature: 20ºC ± 2ºC.
• Room humidity: 45% to 60%
• Air velocity of laminar flow: Horizontal 84+20 ft/min, Vertical 56+10 ft/min.
• Air change not less than 20 per hour.

Environmental cleanliness standard:

It is defined in term of maximum number air borne particle rather than a define particle size in a given volume of air -

Particle	British standard			U.S. Federal Standard
	Class	No./ft3	No./m3	Class	No./ft3	No./m3
0.5 μ	1	86	3000	100	100	3500
5 μ	1	0	0	100	0	0
0.5 μ	2	8495	3,00,000	1000	1000	3,50,000
5 μ	2	57	2000	1000	65	23,000

Cleaning and sanitation for aseptic area:

• Fumigation of the room: this is done with 2.5% savlon in DM water.
• UV irradiation for whole night.

Sterilize products and equipments:

Type	Condition	Materials
Moist heat sterilization	Autoclaving 121ºC at 15 Kg/cm2 for 30 minutes.	Finished products (Ampoule, vial), Rubber closure, container, membrane filter, SS vat, filling machine.
Dry heat sterilization	Heating at 220 ºC for 2 hours. (Double door)	Equipment, empty ampoules, vials, bottles etc.

Water treatment plant:-

In NUVISTA PHARMA water used in liquid division mean purified water, drinking water, normal water, distilled water, WFI (water for injection) all are supplied by sterile division.

Water filtrated by 0.2μ filter. In some cases specially water wastage in washing section in sterile division are reused by filtration and pass through IR. Drinking water also supply in the head office through container.

Fig: Water Treatment Plant Flow Chart of Nuvista pharma Ltd.

Equipment used in Sterile Manufacturin

          ROTA Filling & Sealing Machine for Ampoules, England

           Filtration Machine – Palltronic, Germany

           Manufacturing Vessel (50 Liter)

           Laminar Air Flow Unit, Franz Ziel, Germany.

           Hot Air Sterilizer

           Dissolved Oxygen Analyzer

           Distilled Water Plant

           Linden Autoclave (17) Steam Generator

Sterile section has terminal products and aseptic product producing zone

Terminal products:

The products which are not heat sensitive are called terminal products. The products are auto-claved after filing and sealing. Mainly injections and water for injections are terminal products

Aseptic products: 

The products that are heat sensitive are aseptic products. Autoclaved is done by filtration process. Double filter paper is used. The pore size of first filter paper is 0.5 mµ. The pore size of second filter paper is 0.2 mµ. no bacteria can pass through the pores of 0.2 mµ. Mainly eye drops and insulin are considered as aseptic products

Packaging department

Packaging is the process by which the pharmaceutical products are suitable paked, in such way that they should retain their therapeutic effectiveness from the time of their packaging to consume by the consumers & it also helps to withstand the stress during transport.

Nuvista Pharma Limited has a well-established packaging department.

   Packagings are of two types:

• Primary packaging  (Direct contact with the product eg.alluminium foil)
• Secondary packaging (No contact with the product eg. cartoon case etc)

Primary packaging has two categories:

• Blister packaging
• Strip packaging.

In Nuvista Pharma Blistering machine are:

Ø  HOONG A- Korea

Ø  HOONG B- Korea

Ø  HOONG C- Korea

Ø  FORMPACK ( Injection )

Ø  GANSON-India ( Tablet strip)

Ø   Batch Printing Machine:

Ø  Morico, Japan

Two forms of blistering:

Ø  Alu – alu

Ø  Alu – PVC

Material Used in Packing Section:

Ø     Alu.Foil(Blister/Strip)

Ø     PVC/PVDC Film

Ø     Alu-Alu Foil (Bottom).

Ø     Bottle/Alu.Tube.

Ø     PP Cap.

Ø     Label.

Ø     Unit Carton.

Ø     Insert.

Ø     Plastic Spoon.

Ø     Plastic Cap.

Ø     Stopper.

Ø     Shipping Carton.

Different parts of Blistering machine:

Ø  Heating device

Ø  Forming station

Ø  Filling station

Ø  Sealing station

Ø  Cooling station

Ø  Draw off

Ø  Production tray

Ø  Slit heater

Ø  Code embossing station

Ø  Cutting station

Ø  Coiler

Ø  Conveyor belt

Flow chart of how a Blister machine works during PVC-Aluminium Blister:  

1	2	3	4	5	6	7	8	9	10
Pre heater (110 °C)	Forming plate (Air pressure used)	Hand loading of tab/cap.	Sealing (190 °C)	Cooler (to ensure the product is not exposed to heat)	Batch no.	Cooling	Slitting	Draw	Cut

Important for primary packaging:

Ø  Plug area create pocket by plugging (Alu-Alu), In case of Alu-PVC forming create pocket with the help of air pressure & temp (130º-160 ºC).

Ø  Tablets are manually arranged into production trey.

Ø  In-case of automatic filling, hopper chute channel has two parts

> Chute vibrator

> Feeding roller.

Ø  Top holders contain Aluminium foil.

Ø  Sealing temperature 150 ºC to 210 ºC.

Ø  Scoring is done by slitter. In case of alu-alu, no heat is required. Whereas in alu-PVC 80 ºC to 100 ºC temperature is required.

Ø  Waste coiler coil the wastage remaining after cutting.

Ø  Drawer draws the blistering materials to the cutting area.

The test that are performed by this section for packaging materials are-

Materials Name	Test specification
PVC	Color, width, thickness, weight per unit area etc.
Cotton	Appearance, weight, moisture.
Shipping carton	Weight, diameter, thickness.
Inner carton	Height and level description
Plastic cap	Appearance, weight, length, volume etc
Dropper	Appearance, length, weight and plastic cover.
Tape (adhesive)	Appearance, width, Adhesiveness.
Bottles, Ampoules	Height, volume, capacity, diameter, machine acceptance etc.

Test for Primary packaging:

Ø  Leak test

Ø  Primary quality

Ø  Batch No. and Exp. Date

Ø  Perforation

Ø  Sealing

Ø  Clarity of Pocket

Leak Test:

Leak test is done by the leak test machine after completing blistering and stripping.

Blister / strip are kept under the pored vehicle in the container which contains purified water. Air pressure is given by switching on. Maximum 760 mm Hg pressure can be given. But usually 400 mm Hg is given in case of big pocket and 600 mm Hg is given in small pocket.

Test for secondary Packaging:

Ø  Box, Leaflet, Strip

Ø  Batch No., Mfg. Date, Price

Ø  Color & printing of the Box

When the primary packaging is completed then the tablet or capsule containing blister or strips are checked. And finally the strips or blisters are made ready for secondary packaging.

A fixed number of tablets or capsules are packed into each strip or blister. And a fixed number of strips or blisters are packed into each packet. The packets are

then poured into the box.