Standard Operating Procedure For Product Data Analysis

Purpose:-

To analyse product related data for conformance to specifications, determine trends & to take appropriate actions for improvement.

Scope:-

Product & process quality evaluation at Plant by using suitable statistical techniques.

 Responsibility:-

ù Plant Manager

ù Quality Control Manager

ù Quality Assurance Manager

ù QC Officer

ù QA Officer

Procedure:-

                        The following statistical techniques / tools are being used in the plant.

A)                Sampling Plan for Incoming Materials & Product

For the sampling of incoming goods and produced batches American military standard MIL-STD 105 – E is being used to take the representative samples for inspection / testing of raw materials, packaging components and finished products. Acceptance levels are defined on the basis of these plans and reports are generated for each sample and analysis.

 B)                Trend Analysis

In process Inspection Data

Physical parameters of liquid injections, Liquid syrup, Tablets, Capsules and dry powder injections are checked during the operation at predefined frequencies. Results are plotted on pre-printed trend charts (range charts) are provided with upper and lower allowable limits.

Trends are reviewed regularly during the process by production and IPC staff and are finally reviewed by QC Department before final release.

Finished Products (Active Potency data analysis by Line Graph)

Results of active ingredient’s assay are plotted for each batch on graph sheet to analyze the trend of batch wise product quality.

These plotting are reviewed in GMP committee and quality council meetings. The observations are discussed & appropriate corrective and preventive actions are identified for improvement.

 B)                Variance Analysis:

This statistical technique is applied for the data analysis in

a)                  Liquid Injectable Volume data in QC Lab.

b)                  Powder Injectable drug weight data in QC Lab

c)                  Weight Variation data of OSD (Tablets & Capsules) forms in QC Lab.

d)                 Liquid Syrup Volume data in QC Lab

e)                  Analytical method validation in QC Lab.

f)                   Process Validation in Production

Standard deviations calculated to establish consistency of the relevant process / method.

Quality & Environmental Policy

Standard Operating Procedure for Completing Non-Conformity Report

Purpose      To ensure correct method and sequence is followed in completing a Non-conformity   Report (F-09-02)

Scope       This procedure applies to the non-conformities identified in plant products, processes and services

 Responsibilities

E NCR Originator

E Concerned Department Heads

E Quality Management Representative / QA Incharge

Procedure  E Non-Conformity Report (F-09-02) can be raised as a result of

1)      Routine Inspection / Testing

2)      Customer Complaint

3)      Internal Audit

4)      GMP Audit

5)      Self inspection

6)      Corrective / Preventive Action

A) The Person raising NCR first discuss it with his department head then follow this procedure in processing the Report.

►    Enter date of Report

►    Mark appropriate box on line 1 & 2 based on nature of non-conformity.

►    Enter document number, which is used as standard to identify the non- conformance ( SOP-08--01 etc)

►    Identify person who raised the NCR (Write name of person or customer as applicable)

►    Enter department name, product, or process for which NCR is raised.

►    Non-conformance Write brief description of non conformity with:

a)      Objective evidence

b)      Applicable procedure Para or clause reference (Para 6.2 etc)

c)      Sign and date the non-conformance statement.

B) Root Cause and Result of Investigation:-

The Department Head (where non-conformance was identified) review the NCR and determine the course of action to be followed in consultation with area Incharge. Description of cause and investigation are entered, then corrective action and its implementation is enforced.

C) Corrective Action

The concerned department head is responsible to take corrective actions for identified non conformity & forward completed NCR with support documents; report etc to Quality Management Representative,/ QA Incharge who after review assigns it the sequential No.

D) Close Out

The NCR is closed out after corrective action follow up & review by Quality Assurance Manager / Quality Management Representative / Internal Auditor as applicable.

E) Quality Management Representative / QA Incharge maintains log of all NCRs & send copies of completed NCR to the concerned department. Quality Management Representative present status of non-conformance to management in Management Reviews as per Quality Management System.

F) Each department head should maintain documented record of non-conformances in their department.

Related Documents & Forms

Control of Non Conformity Corrective & Preventive Action            E   (QSP-09)

Product Recall                                                                                    E   (SOP-09-PRL)

Internal Quality Audits                                                                       E   (QSP-10)

Non-Conformity Report                                                                     E   (F-09-02)

Customer Complaint Log Marketing                                                  E   (F-09-01)

Log of NCRs (Product, Process Service)                                           E   (F-09-05)

SOP For Measuring / Monitoring of Noise Level

Scope:-

This procedure provides the guideline for measuring /monitoring of Noise Level at

Purpose:-

To maintain safe noise levels in the plant premises and avoid hearing impairment due               to Excessive noise level.

Responsibility:-

                       

                 Maintenance Incharge.

                 QA Incharge

                 QA Officer

Procedure:-

Excess noise levels (78 dBA) are harmful for the health of human ears and can adversely affect the worker’s performance if exposed to high noise levels over extended period.

To ensure good health & maintain tolerable noise level, noise levels in different areas of Plant are monitored by QA department. Noise level meter with the range of noise detection of 30-130dBA is utilized for the monitoring.

 Incharge QA prepare a plan for noise level monitoring within Plant premises as part of HSE plan. The safe noise level is established for each working area specially production, packing and store areas where noise level due to machine operations could be high. The criteria for monitoring frequency is as follows:

a)      Monitoring noise level at the time of machine/equipment installation.

b)      Monitoring all working areas every quarterly and maintain records.

c)      Monitoring an area based on complaints of excessive noise from the workers/supervisor.

            Maintenance &   QA Incharge operate the meter for monitoring noise levels.

            Operation of Noise Meter:

           Noise level meter has measuring range 30-130dBA frequency range 31.5 Hz

           to 8 KHz and resolution of 0.1dBA. It is a hand held unit with a sensitive microphone,                           extension cord and operated with 9 volt battery

1)        Install the battery by opening battery cover on the unit.

2)        Calibrate the meter before operation.

3)        Ensure meter microphone is dry and protect it from area wind effects by using windscreen around the microphone

1)        Use the extension cable of the microphone. When monitor the noise level to avoid unexpected Noise reflection.

2)        Turn the power switch “ON” on the unit and select the desired “Response time” & “Weighting”. Set response time to “Fast” setting for noise, which consists of short bursts, or for catching peak Sound level. To measure average level use the setting “Slow”.

3)        Select the weighting “A” for general noise level and weighting “C” for measuring noise level of acoustic sound.

4)        Hold the instrument in hand or fix on tripod, pointing the microphone at the noise source. The noise pressure level will be displayed on the meter.

5)        When measuring noise level of different locations in an area use “Max/Min” mode to determine maximum and minimum noise levels of the area.

6)        Press “Max/Min” button once to measure value of maximum noise level. Pressing again will give minimum noise level. At the end press the button third time to exit measuring mode (Max. or Min. symbol will disappear from the screen.)

7)        Turn off the instrument after measurements and record the observations on Noise monitoring record form.

8)        Do not operate or store instrument at high temperature and high humidity environment.

9)        Avoid microphone exposure to excessive vibration.

10)    Remove  battery when instrument is not in use.

11)    Analyze measurement data and discuss in management meeting to determine the corrective & preventive measures and controls for high noise levels.

Standard Operating Procedure for Monitoring of Operational Parameters of Sterile Area

1.         Purpose:-

To maintain environmental conditions within prescribed limit.

To prevent the microbial proliferation.

To Safeguard the product during filling operation

To provide the comfort environment to the operators during filling.

2.         Scope:-

This procedure is followed while maintaining the environmental condition.

3.         Responsibility:-

                        1          HVAC operator

                        2          Microbiologist

                        3.         Incharge Pharmacist

                        4          Sterile Area Operator

4.         Procedure:-

The operational parameters & their limits are as under

STANDARD OPERATING PROCEDURE FOR SPECIFIC TRAINING OF PERSONNEL’S (QAD)

1.       Purpose:

1.1.  The purpose of this SOP is to describe the procedure of specific training of QA personnel.

2.       Scope:

             This SOP is applicable to Quality Assurance Department.

3.       Responsibility:

             Quality Assurance Manager

4.       Procedure:

      4.1. On joining of new personnel to Quality Assurance Department, QA Manager issues job description (JD) to the personnel.

4.2. Specific training program to the new employees (Quality Assurance Officer, Quality Assurance Inspector/ Quality Assurance Assistant) of quality assurance department must covers the following aspects

S/N	Training Topic
01.	Introduction to Quality Assurance.
02.	Awareness on cGMP.
03.	Introduction to Quality Audit.
04.	Market Complaints and Product Recalls.
05.	Self-study of Quality Assurance SOPs.

     4.3. Specific training must be completed within two weeks of the joining of new personnel’s.

     4.4. Assessment of the new personnel must be done after the completion of the training program.

     4.5. Record of such trainings should be kept with the Quality Assurance Department.

    4.6. Besides the specific training of the new employee, QA new employee will also receive continuous trainings as per SOP for the Training of Personnel’s (Ref. # QA/T/01).

5.       List of Recipients:

5.1. Quality Assurance Department.

Flow Chart of Raw Material Store

Clean Room Condition Monitoring (Air Changes)

Objective:-

                        To ensure the air changes in sterile areas (clean Room) as per specification.

 Scope:-

                        It is applicable to the following areas:

§  Liquid Vial Injectabl filling area

§  Liquid Ampoule Injectable area

 Responsibility:-

QA Manager / Incharge

QA Officer

HVAC Engineer

 Procedure:-

In clean rooms, where Injectables are manufactured, it is necessary to periodically monitor the condition of the room. This is done by periodically measuring the velocity of the HEPA filtered air sent into the room and calculating the air changes in the room. This is an important parameter to assess the purging capacity of the air handling system. With the help of Anemometer the velocity of the air is measured at different sites of HEPA Filter out let and from this data the numbers of air changes are calculated.

 Calculation for number of Air changes in Sterile Area

a)      Number of Air inlets in the room = “N”

b)      Area of the inlet surface = Length X Width = “B” square feet

c)      Average Velocity of Air through an inlet = “C” Feet/min

d)     Volume of air = Area of surface X Average Velocity through an air inlet

i.e. = “BX C” Cubic feet / min

            Let “BX C” be denoted by “D”

e)      Volume of the room under consideration = L x W x H = E Cubic feet.

Now number of cubic feet of air through all filters / min = sum of cubic feet / min, of air through each filter in the room.

Thus CFM = D1 + D2 + D3 ………….. DN-1 + DN

Total CFM Di  denoted by “F”

                                                i = 1

f)       Total Cu. Ft of air through all filters in 1 hour = F X 60 CFH (where CFH = Cubic ft / hour)

Now 1 air changes = Total Volume of Room = E. eu.Ft.

Thus E Cu. Ft / Hour corresponds to 1 air change.

F * 60 Cu. Ft / hour corresponds to Air Change =   F * 60  Cu. Ft / Hour    =          Z air change

                                                                                      E Cu. Ft / Hour

 Criteria:-

Air changes / min (Z) should not be less than 20 for Class 10,000 and 5 or more for components preparation room.

Check Frequency:-

 Calculate the air changes for Class 100 area and component preparation room at quarterly frequency.

Calibration of Pressure Gauges, Timers & Temperature Controller / Recorder etc.

Objective:-

This procedure establishes the method to be used for calibration of pressure gauges, timers, temperature controller / recorder etc installed on different equipment in all departments.

Responsibility:-

►    QA Incharge

►    Maintenance incharge

►    All Department Heads

Procedure:-

1. Pressure gauges, timers & temperature controller / recorders are calibrated as per plan (F-07-02). The master list (F-07-01) include these instruments / gauges.

2. In-house & calibration by external source is done as per QSP-07

3. External Calibration arranged by QC Manager through authorized external source & certificate of Calibration is maintained on record.

4. Instruments / Gauges performing within specified range are labeled with calibration stickers.

5. Engineering department coordinates with QA Incharge to implement calibration plan and concerned department maintains record of in-house Calibration.

STANDARD OPERATING PROCEDURE FOR CALIBRATION

1.      Purpose:

1.1.The purpose of this document is to describe the procedure for calibration of machines, equipment’s and apparatus of the facility.

2.      Scope:

2.1.It is applicable in all sections of the plant

3.      Responsibility:

3.1.Quality Assurance Manager

3.2.Quality Assurance Officer

3.3.Section In Charge (Concerned)

4.      Procedure:

4.1.External Calibration

4.1.1.      The Quality Assurance Manager contacts the external party/ company which are authorized to give calibration certificate by some internationally accredited ISO certified company.

4.1.2.      On arrival of the concerned personnel from the relevant calibration company; QA Manager/ Officer shall accompany him/ her within the facility.

4.1.3.      The Quality Assurance Personnel’s provide a list of all the machines, equipment’s, instruments and their accessories which are to be calibrated.

4.1.4.      The calibration team comprising of the personnel’s of the external party/ company along with the quality assurance personnel’s and the relevant section in charge’s calibrate the machines, equipment’s and instruments in the section.

4.1.5.      After performing the calibration, the certified calibrating company shall paste the sticker mentioning that the calibration of the machine/ equipment/ apparatus has been performed.

4.1.6.      After calibration, the certified company verifies the calibration of the machines/ equipment’s/ instruments.

4.1.7.      Following is a list of parameters which require calibration:

                                                                      i.            Rounds Per Minute (RPM)

                                                                    ii.            Pressure Gauges

                                                                  iii.            Temperature Panels

                                                                  iv.            Hygrometers

                                                                    v.            Weight

                                                                  vi.            No. of fills/ minute

                                                                vii.            Machine process controller

4.2.In House Calibration:

4.2.1.      Equipment’s/ instruments/ machines for which in house calibration is to be done are as under:

                                                                    i.            Weighing Scales/ Balances

                                                                  ii.            PH Meter

                                                                iii.            Quality Control Software Based Instruments

4.2.2.      The calibration of weighing balances and PH meters are done in house with a reference standard which is calibrated externally annually.

4.2.3.      In house calibrations for weighing balances/ scales must be done on daily basis.

4.2.4.      Record of in house calibration for all weighing balances present in facility is to be maintained by the quality assurance personnel’s.

4.2.5.      For calibration of PH meter, weekly calibration must be done by the quality assurance personnel’s.

4.2.6.      Quality Assurance Manager is responsible for in house and external calibrations of all the machines/ equipment’s/ instruments/ apparatus.

4.2.7.      It is the responsibility of Quality Assurance Manager to verify that all the machines, equipment’s and instruments are calibrated within the premises.

4.2.8.      Quality Assurance Manager should collect the certificates of calibration and file them properly.

4.2.9.      Any new equipment, machinery or instrument purchased should be calibrated by the certified calibrating company.

5.      List of Recipients:

5.1.Quality Control Manager

5.2.Production Manager

5.3.Quality Assurance Manager

6.      Attached Forms/ Annexure:

6.1.List of equipments, machines and instruments calibrated.

6.2.Daily calibration sheet

STANDARD OPERATING PROCEDURE PROCEDURE FOR HVAC VALIDATION

1.      PURPOSE:

1.1. To verify that HVAC system performance complies with specifications.

2.      SCOPE:

2.1.This SOP is applicable to all areas/ sections where HVAC system is installed.

3.      RESPONSIBILITY:

3.1. Quality Assurance Manager.

3.2. Quality Assurance Officer.

4.       PROCEDURE:

Heating ventilation and air conditioning system Validation tests

4.1.  Air Flow Velocity and Changes  Per Hour

4.1.1.        Scan the area for HEPA Filter, with the anemometer probe. 6 inches from the filter face.

4.1.2.        For ease of experiment, divide the area of the HEPA Filter into four equal, hypothetical grids.

4.1.3.        Record the velocity reading taken at the center of the grids, and at the junction of dividing lines (center of HEPA Filter).

4.1.4.        Calculate the Average Velocity (V in feet per minute) as

                                       V= (V1+V2+V3+V4)                                         Eq. 1

                                                         4

                                       V1= Velocity observation at each point

4.1.5.        Measure the dimensions of each air inlet i.e. HEPA Filter, in feet’s and record it.

4.1.6.        Calculate the Area (A in square feet) of each Air inlet as product of the length and the width as:

                                  A = l × w                                                         Eq. 2

        Where              l = length of inlet

                                 W = width of inlet

4.1.7.        Calculate the Total Air Volume (T in cubic feet per minute) supplied in each zone, by using the formula:

                                    T = A × V                                                      Eq. 3  

        Where                A = Area of particular Air inlet in square feet

                                    V = Average air velocity at particular air inlet in feet per minute

4.1.8.        Calculate the total volume of the room by multiplying length of room, breath of room and height of the room.

                                                        = L × B × H

4.1.9.        Total air change is divided by total volume of the room will give the air change per hour. Fill the record in the form (“HVAC AIR CHANGES FORM” Ref. Format # G/F/99)

4.2. Filter Leak Test.

4.2.1.         Place the anemometer at the front of AHU.

4.2.2.        Check the velocity of air to the all corners of the AHU. The air velocity should be within the higher limit of HEPA filter.

4.2.3.        If the air velocity is more than higher than the limit, change the gas cut to prevent the air leakage.

4.3. Particle Count

4.3.1.        On the air system before one hour of test operation. Take the suitable particle counter and operate it to check the particles in the room at non working operation.

4.3.2.        Collect the information from particle counter and fill them in the format. (ref. Format # G/F/100).

4.3.3.        Operate the particle counter when work is in progress in the area. The particles should be count when more than one hour work has been progressed in the area. Record the data in the format.

4.3.4.        Operate the particle counter for the entire room maintaining grade A, grade B, grade C, and grade D.

4.4. Viable Monitoring.

4.4.1.        Record the results of viable monitoring (ref. Format # MC-002)

4.5. Filter Integrity Test (DOP)

4.5.1.        Filter integrity test (DOP) is performed through an outside source.

4.6. Pressure Difference

4.6.1.        Attach all concerning room (under test) to the manometers which are attached to the wall of adjacent area.

4.6.2.        Turn on the air system, inside tested area and wait to stabilize the pressure in the area.

4.6.3.        Observe the pressure difference from all rooms and from room to room.

4.6.4.        Record the data in the format.(“record of positive pressure” ref. Format G/F/56)

4.7. Recovery (temperature and Humidity)

4.7.1.        Turn off the HVAC system. Check the humidity of the area.

4.7.2.        If the relative humidity of the area is within specification increase the relative humidity by spraying hot water in the area up to 75 %.

4.7.3.        Wait for stabilization of humidity in the area about 75%.

4.7.4.        Operate the HVAC system and note the time. Wait to stabilize the humidity in the area within the specification limit.

4.7.5.        Note and record the time in the format (ref. Format G/F/49 & G/F/50).

4.7.6.        For the recovery test, increase the temperature of the area by using hot air blower in the area and increase the temperature up to 40 C.

4.7.7.        Operate the HVAC system and note the time. Wait to stabilize the temperature in the area within the specification limit.

4.7.8.        Note and record the time in the format.

4.7.9.        Temperature and humidity uniformity test.

4.7.10.    Place the calibrated thermometer on the different locations.

4.7.11.    Operate the HVAC system and note the time. Wait for stabilization of temperature in the area within the specification limit.

4.7.12.    Check and record the temperature of the area in format.

4.7.13.    Place the calibrated hygrometer on different locations.

4.7.14.    Operate the HVAC system and note the time. Wait to stabilize the humidity in the area within the specification limit.

4.7.15.    Check and record the humidity of the area in format (ref. Format G/F/49 & G/F/50)

5.       LIST OF RECIPIENTS:

1.1. Quality Assurance Manager

1.2. Maintenance Manager

  

6.      Attached Forms/ Documents:

6.1.Temperature & Humidity Record (ref. Format #)

6.2.Pressure record (ref. Format # )

6.3.Viable count record (ref. Format #)

6.4.DOP test certificates