Thursday, May 26, 2016

Autoclave validation


Sterilization process in pharmaceutical industry in an autoclave will be considered qualified for consistent and reliable performance (validated) on successful completion of the following tests–
• Bowie – Dick Test for steam penetration (3 trails).
• Empty Chamber Heat distribution studies (3 trails) with temperature mapping probe at different locations of the sterilizer chamber.
• Loaded chamber heat Distribution & penetration studies (3 trails) for each sterilization load of fixed loading pattern –
1) Sterile area garments (20 number Garments packs, Each pack contains 01 Nos. Boiler suit, 01 Nos. Headgear, 02 Nos booties, 01 pairs gloves)
2) Glassware (S.S Mannifold holder (06 holder) 02 Nos, Sampling unit of Compressed air 02 Nos, 500 ml sampling bottles 10 Nos, 250 ml sampling bottles 25 Nos, 04 Nos S.S Bin.)
3) Media (SCDA Medium – 500 ml 09 Nos. Conical flask, SCDM – 100 ml 20 Nos. tubes, FTM – 100 ml 10 Nos. tubes, MSA – 250 ml 01 Nos Conical flask, CA – 250 ml 01 Nos Conical flask, BGA – 250 ml 01 Nos Conical flask, BSA – 250 ml 01 Nos Conical flask, MCA – 250 ml 01 Nos Conical flask, Peptone Water – 500 ml 06 Nos. Conical flask.)
With temperature mapping probes along with Biological Indicator (Geobacillus stearothermophillus spore vials containing 10^6 or more spores per vials) inside the innermost possible layer of the load subjected for sterilization.
• Estimation of the F0 Value achieved during the sterilization hold period at each temperature mapping probe.
To qualify these tests the equipment should fulfill the acceptance criteria described in the individual test procedures. After completion of the qualification tests all the data generated will be compiled together to evaluate ability of the steam sterilizer to sterilize different components at the set parameters and set loading pattern.
A) Bowie – Dick test for Steam Penetration
Objective
Objective of this test is to ensure that the vacuum pulses applied the sterilization hold period are sufficient to remove the entrapped air so as to facilitate rapid and even steam penetration into all parts of the load and maintaining these conditions for the specified temperature holding time (17 minutes at 121 deg.C)
If air is present in the chamber, it will collect within the Bowie – Dick test pack as a bubble. The indicator in the region of the bubble will be of different color as compared to the color on the remaining part of the test paper, because of a lower temperature, lower moisture level or both. In this condition the cycle parameters to be reviewed and the normal sterilization cycles to be modified accordingly.
Bowie – Dick cycle should be normally preceded by a warm – up cycle, as the effectiveness of air removal may depend on all parts of the sterilizer being at working temperature.
Procedure
1. Record the set parameters for the Bowie – Dick test cycle in The Annexure.
2. Place one Bowie – Dick test pack near the drain of the sterilization chamber.
3. Select cycle Bowie – Dick on the control panel & operate the steam sterilizer.
4. The print out taken during the Bowie – Dick test cycle & the Bowie – Dick test indicator should be preserved.
5. Compile the observation made during the qualification test for complete evaluation of the system.
Acceptance Criteria
The Bowie – Dick Test indicator should show a uniform color change, non – uniform change and/or air entrapment (bubble) spot on the pattern indicates inadequate air removal from the sterilization chamber.
Observation & Results
Record the observation and results in format. 

B) Empty Chamber Heat Distribution Studies
Objective
Objective of this test is to ensure that, The sterilizer is capable of attaining a temperature of 121 deg.C during the sterilization hold period with steam pressure of 1.1 to 1.2 kg/cm2.
Temperature spread with in the range of 121 deg.C to 124 deg.C during sterilization cycle will demonstrate the uniform heat distribution within the chamber.
Any location where the temperature indicator is placed, not achieving minimum sterilization temperature of 121deg.C through out the sterilization temperature hold will be considered as cold spot.

Procedure
1.0 Record the set parameter for the sterilization cycle to be operated during the test for empty chamber heat distribution study, in the Annexure.
2.0 Pass minimum 16 no. Temoerature mapping probe into chamber through the port of the sterilizer. Seal the port with silicone sealant so that steam leakage does not take place. Suspend the probes in the chamber in different position so that probes do not touch any metallic. Record the position of the probes in a respective schematic form.
3.0 Connect the probes to a suitable autoclave data logger, which can scan and print the actual temperature observed at different locations with respect to time.
4.0 Operate the steam sterilizer and also start the autoclave data logger to record actual temperature within the sterilization chamber with respect to time.
5.0 When the sterilization cycle completes, 1) Collect printout of the sterilizer and preserve as Annexure. 2) Download the data-analysis and printing. Record the temperatures observed at different locations in the Annexure.
6.0 If the empty chamber heat distribution study is acceptable perform three consecutive runs to demonstrate cycle and sterilizer reproducibility.
7.0 Compile the data generated during the qualification test for complete evaluation of the system.
Acceptance Criteria
There should be uniform distribution of heat in the sterilizer chamber during the sterilization hold period and the temperature at each temperature mapping probes should be within the range of 121 deg.C to 124 deg.C during the sterilization hold period.
Observations and Results
Record the observations and results in formats.

C) Loaded Chamber Heat Distribution & Penetration Studies
Objective
Objective of this test is to ensure that, the steam is sufficiently penetrating into the innermost portions of the load subjected for sterilization to achieve desired temperature of 121 deg.C during the complete sterilization hold period with steam pressure of 1.1 to 1.2 kg.cm2.
If Sterilization temperature (121 deg.C) is not achieved through out the cycle, load configuration or size of the load has to be reviewed and cycle to be repeated.
Temperature spread within the range of 121 deg.C to 124 deg.C during sterilization hold period indicate that, uniform heating process which is achieved in the empty chamber heat distribution study is not affected by load. There could be the possibility of lag period for attaining 121 deg.C during heat penetration runs as the probes are placed deep into the load.
Any location where the temperature indicator is placed, not achieving minimum sterilization temperature of 121deg.C during sterilization temperature hold period will be considered as cold spot.

Procedure
1.0 Record the set parameter for the sterilization cycle to be operated during the test for loaded chamber heat penetration study in the Annexure.
2.0 Pass minimum 16 no. Temperature mapping probe into chamber through the port provided. Seal the port with silicone sealant so that steam leakage does not take place. Place the probes inside the load components, which are supported to be most difficult points for steam penetration, also place biological indicator along with temperature mapping probe (12 Nos.). Record the position of the probes and biological indicators in a representative schematic form.
3.0 Connect the probes to a suitable data logger, which can scan and print the actual temperature with respect to time.
4.0 Operate the steam Sterilizer and also start the data logger to record the actual temperatures within the sterilization chamber with respect to time.
5.0 When the sterilization cycle completes, 1) Collect printout of the sterilizer and preserve as Annexure. 2) Download the data-analysis and printing. Record the temperatures observed at different locations in the Annexure. 3) Aseptically collect the exposed biological indicators and send the indicators to microbiology lab for further incubation and observed the results.
6.0 If the load penetration study is acceptable perform three consecutive runs to demonstrate cycle and sterilizer reproducibility.
7.0 Compile the data generated during the qualification test for complete evaluation of the system.
Acceptance Criteria
There should be uniform distribution & penetration of heat in the load subjected for sterilization during the sterilization hold period and the temperature at each temperature mapping probe should be within the range of 121 deg.C to 124 deg.C during the complete sterilization hold period.
Observations and Results
Record the observations and results in formats enclosed as Attachement

D) Bio-challenge studies
Objective
The steam sterilization process in pharmaceutical industry, when challenged with Geobacillus stearothermophillus Biological indicator spore vial, spore population of NLT 106 spores/vial, should reduce bacterial load by mean of Sterility Assurance Level (SAL) 106
On incubation of the loaded biological indicator, if growth is observed, then the sterilization cycle parameters to be reviewed.
Procedure
1.0 Determine the initial counts of biological indicator.
2.0 Collect the exposed indicator (during the loaded chamber heat distribution & heat penetration studies) by using sterile forceps and scissors in a 100 ml beaker and then send to microbiology lab for incubation (Incubate the vial at 55 to 60 deg.C for 48 hours)
3.0 Keep one vial as a negative control provided by the Mfg of biological indicator as well as one vial as a positive control (unexposed vial biological indicator).
4.0 Observe any growth (purple color – sterile, yellow color – Non sterile) in the vial daily. Record the observations on daily basic in the Annexture.
5.0 Compile the data generated during the qualification test for complete evaluation of the system.
Acceptance Criteria
No bacterial growth should observed during the incubation period of 48 hours at 55 to 60 deg.C.
Observations and Results
Record the observations and results in formats enclosed as Attachement.

E) Estimation of F0 Value
Objective
The calculated F0 value should not be less than the biological F0 value at all temperature mapping locations during the sterilization hold period.
Procedure
1.0 Record the temperature at all temperature mapping probes during the sterilization hold period in the Annexure.
2.0 Calculate the F0 value at each temperature mapping probe by using the equation as below.
3.0 Record the F0 value (Results) in the Annexure.
4.0 Compile the data generated during the qualification test for complete evaluation of the system.

Calculation
F0 = dt S10(T-121)/z
Where
dt = Time interval between two following temperature measurements (1 minutes).
T = The observed Temperature at that particular time.
Z = The change in the heat resistance of Geobacillus stearothermophillus spores as temperature is changed (10 deg.C). 
Acceptance Criteria
The calculated minimum F0 value (by equation) should be more than biological F0 value for the biological indicator vial exposed for the bio-challenge studies.
- The biological F0 value for the specific biological indicator spore vial is calculated as per the following equation
F0 = D121 (Log A – Log B)
Where
D121 = D value of the of the biological indicator at 121 deg.C.
A = Biological indicator concentration or spore population.
B = Desired level of non – sterility. (10 deg.C)

Tuesday, May 17, 2016

Stability Studies


Know different climatic zones by ICH in the world for stability conditions including Temperate, Mediterranean / subtropical, Hot dry, Hot humid / tropical and hot & higher humidity zones.

The climate is different in all the countries in the world. Stability study of the pharmaceutical drug should be done according to the climatic conditions of the country. According to the climate, world is divided into five different zones.

ICH Stability Zones
Zone Type of Climate

Zone I :- Temperate zone

Zone II :- Mediterranean/subtropical zone

Zone III:- Hot dry zone

Zone IVa :- Hot humid/tropical zone

Zone IVb:- Hot/higher humidity

These zones are created due to difference in temperature and humidity. Following are the climatic conditions for these zones.

Long Term Testing Conditions

Climatic Zone
Temperature
Humidity
Minimum Duration

Zone I :- 21ºC ± 2ºC, 45% RH ± 5% RH, 12 Months

Zone II :- 25ºC ± 2ºC, 60% RH ± 5% RH, 12 Months

Zone III:- 30ºC ± 2ºC, 35% RH ± 5% RH, 12 Months

Zone:- IVa, 30ºC ± 2ºC, 65% RH ± 5% RH, 12 Months

Zone IVb: 30ºC ± 2ºC, 75% RH ± 5% RH, 12 Months

Refrigerated:- 5ºC ± 3ºC, No Humidity, 12 Months

Frozen: -15ºC ± 5ºC, No Humidity, 12 Months

Accelerated and Intermediate Testing Conditions

Climatic Zone

Temperature Humidity Minimum Duration:-
Accelerated Ambient:- 40ºC ± 2ºC, 75% rH ± 5% rH, 6 Months

Accelerated Refrigerated:- 25ºC ± 2ºC, 60% rH ± 5% rH, 6 Months

Accelerated Frozen:- 5ºC ± 3ºC, No Humidity, 6 Months

Intermediate:- 30ºC ± 2ºC, 65% rH ± 5% rH, 6 Months.

Quality Assurance Interview Question

  1. Define quality assurance
  2. Difference Between Quality assurance and Quality control
  3. What is cGMP?
  4. Difference between cGMP and GMP
  5. ICH Guidelines
  6. Difference between validation and calibration
  7. What is IQ OQ PQ DQ
  8. Cleaning validation 
  9. Some times they will ask you principle of various instruments and equipments such as HPLC, GC UV etc., so just go through it.
  10. Standard Operation Procedure general questions (what is SOP, type of SOP? etc.,)
  11. General questions on BMR
  12. General question on BPR
  13. Types of Regulatory bodies.
  14. How many guidelines do you know?
  15. Have you ever faced audit?
  16. What is audit?
  17. Types of audit?
  18. What is deviation?
  19. What is Out of specification or Out of trend?
  20. Sampling procedure 
  21. Sampling methods.
  22. In process quality control test.
  23. Stability studies, short term and long term.
  24. Stability or climatic zones.
  25. Water validation phase I , II and III time period.
  26. How to do Swab analysis?
  27. HVAC system general questions.
  28. These are some of the questions which they will ask you, but if you are experienced person , then they will ask you about your previous work,
  29. What type of work you have done in your previous organization?
  30. Which type of work , you will perform better.
Points to remember:
  1. Don't try to give wrong answers, if you do not know the answer then tell them frankly , that you don't know the answer.
  2. In walk in interview sometimes they are taking written test to shortlist the candidates.
  3. If you answer wrong then they will ask you more about that particular topic.
  4. Before going to any company for interview, just make a list that what type of products they are manufacturing, for example, if they are manufacturing tablets, capsules or parental products, then go through some basic questions  such as ,. types of defects in tablets, ph of parental products, or capsule is made up of? etc,

General Interview Questions in pharma industry:


    Image results for interview questions
  1. Introduce yourself 
  2. Tell me about yourself
  3. Your strength and weakness
  4. Why do you want to join us?
  5. How long will you stay with our company?.
  6. Your achievements
  7. Are you planning for further studies?
  8. Do you know any one in this company?
  9. Are you fresher or experienced?
  10. Your work experience?
  11. Why should we hire you for this job?
  12. What salary are you looking for?
  13. Why you left the previous job (if experienced)?
  14. What type of major challenges and problems have you faced?
  15. Where do you see yourself in 5 years?


Friday, May 13, 2016

ICH Guidelines

Following is the list of guidelines:

Q1A(R2) - Stability Testing of New Drug Substances and Products

Q1B - Stability Testing: Photostability Testing of New Drug Substances and Products

Q1C - Stability Testing for New Dosage Forms - Annex to the ICH Harmonised Tripartite Guideline on Stability Testing for New Drugs and Products

Q1D - Bracketing and Matrixing Designs for Stability Testing of New Drug Substances and Products

Q1E - Evaluation for Stability Data

Q1F - Stability Data Package for Registration Applications in Climatic Zones III and IV

Q2(R1) - Validation of Analytical Procedures: Text and Methodology

Q3A(R2) - Impurities In New Drug Substances

Q3B(R2) - Impurities in New Drug Products

Q3C(R5) - Impurities:  Guideline for Residual Solvents

Q4 - Pharmacopoeia

Q4A - Pharmacopoeial Harmonization

Q4B - Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions

Q4B Annex 4A(R1) - Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Microbiological Examination of Non-Sterile Products: Microbial Enumerations Tests

Q4B Annex 4B(R1) - Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Microbiological Examination of Non-Sterile Products: Test for Specified Micro-Organisms

Q4B Annex 4C(R1) - Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Microbiological Examination of Non-Sterile Products: Acceptance Criteria for Pharmaceutical Preparations and Substances for Pharmaceutical Use

Q4B Annex 1(R1) - Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Residue on Ignition/Sulphated Ash

Q4B Annex 2(R1) - Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Test for Extractable Volume of Parenteral Preparations

Q4B Annex 3(R1) - Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Test for Particulate Contamination: Sub-Visible Particles

Q4B Annex 5(R1) - Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Disintegration Test

Q4B Annex 6(R1) - Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Uniformity of Dosage Units

Q4B Annex 7(R2) - Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Dissolution Test

Q4B Annex 8(R1) - Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Sterility Test

Q4B Annex 9(R1) - Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Tablet Friability

Q4B Annex 10(R1) - Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Polyacrylamide Gel Electrophoresis

Q4B Annex 11 - Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Capillary Electrophoresis

Q4B Annex 12 - Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Analytical Sieving

Q4B Annex 13 - Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Bulk Density and Tapped Density of Powders

Q4B Annex 14 - Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Bacterial Endotoxins Test

Q4B - Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions

Q5A(R1) - Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin

Q5B - Quality of Biotechnological Products: Analysis of the Expression Construct in Cells used for Production of r-DNA Derived Protein Products

Q5C - Quality of Biotechnological Products: Stability Testing of Biotechnological/Biological Products

Q5D - Derivation and Characterisation of Cell Substrates Used for Production of Biotechnological/Biological Products

Q5E - Comparability of Biotechnological/Biological Products Subject to Changes in their Manufacturing Process

Q6A - Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances

Q6B - Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products

Q7 - Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients

Q8(R2) - Pharmaceutical Development

Q9 - Quality Risk Management

Q10 - Pharmaceutical Quality System

Q11 - Development and Manufacture of Drug Substances (Chemical Entities and Biotechnological/Biological Entities)

Wednesday, May 4, 2016

DATA INTEGRITY - Why it is so Important???

Data Integrity Means: 
   
- Accurate and reliable data and Information


-Ensuring data trustworthiness and reliability

-The degree to which a collection of data is complete, consistent and accurate

We have To learn what may go wrong which lead to data integrity issues in cGMP. We Will learn phase wise and day to day cases.To understand DATA Integrity let understand requirement and concept Recent regulatory agency observations steer industry to the conclusion that there can be severe penalties for not having data quality that leads to product quality. Data quality may be explained by a simple and straight forward equation:  Data Integrity + Data Management = Data Quality. Data quality is mutually dependent on both data integrity and data management.Data management is the process by which we create, control, manage, utilize, and maintain data integrity.Data integrity is the foundation of Data Quality.Conversely, data quality with data integrity but without good data management lacks control of data.Similarly data management without data integrity will lack the elements necessary to have data quality.Data integrity can be expressed in terms of the acronym "ALCOA+” which represents attributable, legible, contemporaneous, original, accurate, complete, consistent, enduring, and available.These attributes must be understood and applied to data integrity with good data management. It is only through both that data quality can be achieved. These attributes explained with next time in elaborated manner.

ALCOA:

A = ATTRIBUTABLE
Attributable data linked to the individual who created or recorded the data.
Person’s signature or initials provide attribution to the DATA, that this data recorded, prepared, analyzed or done by, verified by, reviewed by, checked by the individual. In simple words, the data having traceability of the individual who performed the activity.For computerized systems, making data attributable is the utilization of a unique user with an associated private password linked to the individual’s identity.Examples are shared below which leads to data integrity issues
1) The Person/Individual not present in the company however signed the activity on that date.
2) Sharing of Passwords.
3) Generic user Ids.
4) Deletion of Data
5) Different data Folders
6) Individual data files
7) No Audit trail
8)The Computerized system doesn't having control to capture the changes (who, when and why).
9)  Entering the Area  without having authorization of that  Area.
10) User access rights which prevent (or audit trail) data amendments.
11) The use of scribes to record activity on behalf of another operator/Analysts should be considered only on an exceptional basis and only take place where:
> the act of recording places the product or activity at risk, e.g. documenting line interventions by aseptic area operators;
> to accommodate cultural or mitigate staff literacy/language limitations, for instance, where an activity is performed by an operator, but witnessed and recorded by a supervisor or officer
.
L= LEGIBLE
Legible data are clear, concise, and readable.  Changes to legible data must not hide or obscure the original record.The data should be understandable, means the raw data shall be write in such a way that it should be easily understandable.

Which activity may Leads to Data Integrity Issues
1)Overwriting.
2)Usage of Fluids, eraser, hiding any written information for unfair means.
3) All Electronic data (raw data, Audit trail) must be able to be reviewed and understood in human readable form. 
4) The correct metadata should be linked to each action(for example, Weight prints, pH prints etc.)

= CONTEMPORANEOUS   
Contemporaneous means data must include the date and time of its measurement or action.  For computerized systems all data, including metadata, must be related to an action or event.

Which activity may Leads to Data Integrity issues
1) Record data first in unofficial documentation (e.g. on a scrap of paper) and later transfer the data to official documentation (e.g. the laboratory notebook). Instead, original data should be recorded directly in official records, such as approved analytical worksheets, immediately at the time of the GxP activity.

2) It is improper to back date or forward date a record. Instead the date recorded should be the actual date of the data entry. Late entries should be indicated as such. If a person makes mistakes on a paper document he or she should make single-line corrections, sign and date and provide reasons for the changes and retain this record in the record set.

3) Stand-alone computerized systems are provided with full administrator rights to the workstation operating systems on which the original electronic records are stored, this may inappropriately grant permissions to users to rename, copy, delete files stored on the local system and to change the time/date stamp.
4) Difference in time more than ±1 min form the satellite watch to the Clock represents  the time in the Instrument/Equipment.

O= ORIGINAL
Original data is the original record or a certified copy.Original data and/or certified true and exact copies that preserve the content and meaning of the original data should be retained as such, original records should be complete, enduring and readily retrievable and readable throughout the records retention period.Original data include original electronic data and metadata in stand-alone computerized laboratory instrument systems.(e.g. UV/Vis, FT-IR, ECG, LC/MS/MS, hematology and chemistry analyzers, etc.), original electronic data and metadata in automated production systems(e.g. automated filter integrity testers, SCADA, DCS, etc.), original electronic data and metadata in network database systems (e.g. LIMS, ERP, MES, eCRF / EDC, toxicology databases, deviation and CAPA databases, etc.), handwritten sample preparation information in paper notebooks, printed recordings of balance readings, electronic health records, paper batch records.

Which activity may Leads to Data Integrity issues
1)Data and document retention arrangements should ensure the protection of records from deliberate or inadvertent alteration or loss. Secure controls should be in place to ensure the data integrity of the record throughout the retention period. Archival processes should be defined in written procedures and validated where appropriate.
2)  Data collected or recorded (manually and/or by recording instruments or computerized systems) during a process or
procedure should show that all the defined and required steps have in fact been taken and that the quantity and quality of the output are as expected, enable the complete history of the process or material to be traced and be retained in a comprehensible and accessible form. That is , original records and/or certified true copies should be complete, consistent and enduring.
3) If true copies of original paper records are made by scanning the original paper and converting to an electronic, image, such as pdf, then additional measures to protect the electronic image from further alteration are required (e.g. storage in secure network location with limited access only to electronic archivist personnel, measures to control potential use of annotation tools or other means of preventing further alteration of the copy).
4)  Preserving the original electronic data in electronic form is also important since data in dynamic format facilitates greater usability of the data for subsequent processes. For example,temperature logger data maintained electronically facilitates subsequent tracking and trending and monitoring of temperatures in statistical process control charts.
5) Trial Injections of sample.
6)   Unauthorized folders in electronic systems in which some GMP data is there.
7)Reprocessing of  data without authorization.
In addition to the option of creating certified true copies of original electronic data as verified back-up copies that are then secured in electronic archives, another option to create a certified true copy of original electronic data would be to migrate the original electronic data from one system to another and to verify and document that the validated data migration process preserved the entire content, including all meaningful metadata, as well as the meaning of the original electronic data.
9) Duplicate/repeat analysis without using QMS Investigation and assessment of risk.

A= ACCURATE
Accurate data is correct through the system’s lifecycle.  It indicates the same value and its correct meaning. The term “accurate” means data are correct, truthful, valid and reliable.For both paper and electronic records, achieving the goal of accurate data requires adequate procedures, processes, systems and controls that comprise the quality management system. The quality management system should be appropriate to the scope of its activities and risk-based. Controls that assure the accuracy of data in paper records and electronic records include, but are not limited to qualification, calibration and maintenance of equipment, such as balances and pH meters, that generate printouts;Validation of computerized systems that generate, maintain, distribute or archive electronic records;Validation of analytical methods;Validation of production processes;Review of GxP records;Investigation of deviations and doubtful and out-of-specifications results;
Which activity may Leads to Data Integrity issues
 1) The entry of critical data into a computer not by an authorized person (e.g. entry of a master processing formula) requires an independent verification and release for use by a second authorized person. For example, to detect and manage risks associated with critical data, procedures would require verification by a second person, such as quality unit personnel, of: calculation formulae entered into spreadsheets; master data entered into LIMS such as fields for specification ranges used to flag out-of-specification values on the certificate of analysis; other critical master data, as appropriate. In addition, once verified, these critical data fields would be locked to prevent further modification, when feasible and appropriate.
2) To ensure the accuracy of sample weights recorded on paper printout from the balance, the balance would be appropriately calibrated and maintained prior to use. In addition, synchronizing and locking the metadata settings on the balance for the time/date settings would ensure accurate recordings of time/date on the balance printout.
 3) first data failed specs, retest data passes specs, lab investigations are inadequate or non-existent, but retest data is submitted to the application, anyway.

C = COMPLETE
Complete data includes all data from actions taken to obtain the final result.  Complete data includes all metadata generated for each action taken including audit trails.Data management controls need to include procedural controls that ensure that all data are captured and maintained.  In the laboratory this data should include all runs -- not just those that passed.  The data should not only have the values but also units where appropriate.  Procedures must provide the controls when data not used to calculate a final result must be scientifically justified.

C = CONSISTENT
Consistent data shall be created in a manner that can be repeated following a logical sequence of activities based on the method or procedure.  Consistency can be defined throughout the lifecycle of data.Procedural controls are essential to successfully creating consistent data.  If users are following prescribed methods the likelihood that data can be recreated in a repeatable and consistent manner is much higher. Better efficiencies can often be realized when the method of capture is refined by the users who follow the procedural control on a regular basis.Efficiencies can be built into your process wherein you address multiple data integrity elements simultaneously.  For example, time stamps can be used to indicate that adequate time has elapsed to complete process tasks adding both consistent and contemporaneous data integrity elements into a single process.

E = Enduring 
Enduring data must be protected from loss, damage, and/or alteration and must be available throughout the defined retention period. Data should be stored on a medium that endures the entire retention period.  Data backups should be stored at a different location than the original/raw data.  Procedural controls must monitor your data.  Confirmation that data can be recovered and read throughout the retention period must be tested periodically as appropriate.

A= AVAILABLEAvailable data are readily retrieved throughout the lifecycle of the system, or the appropriate retention period.  Data must be available in human readable form. Considerations must be taken to ensure that data is always available in a timely manner.  Procedures must identify how data is stored, where it is stored, and how it can be retrieved.  As systems improve, system owners need to ensure that all data are available as systems are upgraded  In order to successfully produce good quality data, we must embody the concept that good data quality is an output of both data integrity and data management.  The appropriate starting point is to understand and apply the elements of data integrity and implement good efficient data management.  It is only through both that data quality can be achieved. 

Reference : Data integrity Hand book

IMPORTANCE OF NOTICE PERIOD

Image result for notice period
The notice period is the time period between the receipt of the letter of dismissal and the end of the last working day. This time period has to be given to anemployee by his employer before his employment ends. It also refers to the period between resignation date and last working day in the company when an employee resigns.

Whether you have decided to leave or have been asked to, here's a list of things to do and avoid when you are serving the notice period.

Boss first, others next
If you have decided to leave, be graceful and speak to your boss first. It is both professional and wise to put your resignation down in writing only after your boss has given the go ahead. This gives him time and space to process the information, plan the next steps and even make a counter offer. Ask how your exit should be communicated to others and let him or her decide what works best. If the firm has down sized you, your boss is already in the picture. Seek his inputs and views on what happened and what could have been done.
It's about work not play
Once your departure from the company and last working day is confirmed, you can make your plans. Act with dignity as you are still in employment. Your reputation will depend on how you behave now. Be professional and avoid the folly of mentally checking out of your office during your notice period. Maintain your professional routine. Discuss and negotiate work expectations with your boss and team and then exceed expectations in both scope and deadlines. If you need time off during this period, reassure the firm on your commitments.
Knowledge transfer
Your employer may want you to complete all existing projects before you leave. However, given the limited duration of your notice period vis-a-vis the length of the project, that may not be practical. A more reasonable expectation is a full knowledge transfer to the person or team that will take over your role and responsibilities. Start off with meeting your replacement and setting an agenda for handing over information. Introduce your replacement to your team, clients and vendors and formally inform them of the change in role. Share details of your weekly progress with your boss and make sure other stake holders, including accounts and HR, are also in the loop. A great knowledge transfer will continue to burnish your reputation after you leave.

Thank yous and byes
Apart from official requirements, take time out for the professional relationships you have built. Make a list of people you need to thank personally or writing an email. Spread out your communication over the last two weeks so that you do not miss out in the final days. Prepare a nice farewell speech in case your team gives you a formal send-off party. Leave out the unpleasant memories while you share achievements, contributions by others and stories of your personal growth. People won't remember what you said but they will remember how you made them feel. So be gracious and exit on a high because your future employers will speak to former colleagues when they run a verification check on you for senior roles.
 
References
Towards the beginning of your notice period, speak to your supervisors, HR and senior colleagues and sound them out to write reference letters. HR managers are generally permitted to give standard experience letters. Make sure they include details of joining, relieving, last designation and, where possible, whether the firm is open to re-hiring you. Even if you have your next job tied up, seek references as long-term investments.

Documentation and finances
Obtain a clearance certificate from all concerned stakeholders. Retain a soft copy of the no-dues certificate. Transfer all personal data and contacts from your office computer to your own devices. Obtain fresh insurance covers as your employer-sponsored insurance covers will lapse once you leave. Discuss your gratuity if you have completed 5 years. Transfer your PF account or withdraw it if you are unemployed for over two months. Calculate your commissions, pending salaries, applicable bonuses, reimbursement bills and encashment of leaves with your HR before you leave so that your final settlement is error free.

Garden leave
If you are a banker or working at a strategic level then you might be asked to go on garden leave. Here you are expected to stay at home and not join another firm for a couple of months. This ensures the strategic value of the information that you hold degrades with the passage of time and is of lesser use to competitors who may employ you. When you are on garden leave, remember that you are on contract with your present employer and thus legally bound not to work or share your information or skills with any other firm.

Plan the future
You may have a job offer in hand and can choose to use your spare time to try and get something better. If you do not have an offer and need a job, then invest most of your time in your job search. If you have an interview that clashes with work hours, your present employer is likely to grant leave and support you in your job search. Finally, you may choose to upgrade your skills or study further. Use this time to explore your options and plan your finances for the study break.
During my short span of time in industry as an HR professional, we met lot of incidents where sometimes employees care for their organizations but they did not get the enough support and care from organizations and leads to a change or in some cases organizations understand their employees well but employees are not able to change their attitude. As HR professionals, we act as a medium between the employees and the organizations where we need to maintain the harmonious relation and need to work in the benefit of organization as well as employees.
Out of those a big question is on importance of Notice period pokes me every time. An employee has to serve the notice period of 1 month or 2-3 months that depends on company policies, but the main logic about this practice is to hire an employee within that time period so that previous employee handover the charge to new employee for smooth working and company’s work doesn’t suffer. As per industry norms, when an employee resigns then he /she has to serve a notice period for 1 month or as per the requirement of the organization. But my question is IT WORKS OR NOT? Means what exactly we want by this exercise/practice, is it fruitful/purposeful or not?
Most of the organizations were having the trend of 1 month notice period but today’s scenario it is coming into fashion that employees are asked to serve three months of notice period. Is there any worth of this? An employee when takes these decisions that he/she is going to put resign most of the time he/she has a mind set to leave the organization anyhow. But in some cases there is a possibility to retain the employees. But if we are going to retain employee, notice period doesn’t start because all this process we follow before accepting his/her resignation.
In my point of view, if someone has no interest to work with the companies then will he/she work with proper attention or full of his/her interest with in his/her notice period? And we people want them that they need to stay with us for maximum time period as organizations are throwing 3 months of notice period. Most of the employees come for only serve the notice period in the organization not with the mind set of working what organizations expect from them. If we don’t get any satisfactory work from them then what is the reason to give them a complete compensation for which they are not eligible in their notice period because they are not performing on that level for which we are paying them. In this case, rather to pay resigned employees, we should buy outs the notice period amount for new hires so that we can bring them to join us in minimum period of time.
In their notice period, they can go for an unethical practice also which can be harm to work or prestige of the department as well as the organization, it is rare but still it can be. In my point of view rather than to throw on them 3 months or 2 months of notice period we should focus on hire new candidate for the same position so that we can save our resources or money to spend on those employee who are not interested to be with the organization and relieve them within the least time period so that they will feel free and can go without any burden.
By this, my objective is not to blame any employee or don’t want to prove that we can’t trust on ex employee but again being an HR person my responsibility is to save and look after my companies resources and the same time to make feel employees good about organization. So, against a long notice period, one month notice period is very much sufficient for every position in every industry.

Tuesday, May 3, 2016

AQL (Acceptance Quality Level) and inspection severity

The Acceptance Quality Level is a statistical tool to inspect a particular sample size for a given lot and set maximum number of acceptable defects. In order words, it is the worst tolerable process average when a continuing series of lots is submitted for acceptance sampling.

The AQL has been recently renamed from “acceptance quality level” to “acceptance quality limits”. It is the limit that customer sets which is not really acceptable. Customers prefer zero defect products or services, which is the ideal acceptable quality level. However, customers arrive and set acceptable quality limits based on business, financial and safety levels.

The AQL of a product would vary from industry to industry. Companies dealing with medical tools would have more stringent AQL, as acceptance of defective products could result in health risks. Companies usually face two possible situations, to weigh against; cost involved in testing stringent acceptable levels or spoilage due to lower acceptable levels with a potential cost of product recall. AQL is an important statistic for companies seeking Six Sigma level of quality control.

Failure to meet the requirements of customers with respect to quality is termed as defects. In practice, there are three categories of defects

Critical Defects: Defects, when accepted could lead to harm the users. Such defects are totally unacceptable. It is defined by 0% AQL
Major Defects: Defects usually not acceptable by the end users, as it is likely to result in failure. The AQL for major defect is 2.5%
Minor Defects: Defects, which are not likely to reduce materially the usability of the product for its intended purpose but slightly differs from specified standards. Some end users still go ahead and buy such products. The AQL for minor defects is 4%
What the standard says about inspection level:

The inspection level designates the relative amount of inspection. Three inspection levels, I, II and III for general use. Unless otherwise specified, level II shall be used. Level I may be used when less discrimination is needed or level III when greater discrimination is required.

Four additional special levels, S-1, S-2, S-3 and S-4 are also given in Table 1 and may be used where relatively small sample sizes are necessary and larger sampling risks can be tolerated.

What the standard says about inspection severity:

Normal inspection: use of a sampling plan with an acceptance criterion that has been devised to secure the producer a high probability of acceptance when the process average of the lot is better than the acceptance quality limit.

NOTE Normal inspection is used when there is no reason to suspect that the process average differs from an acceptable level.

Tightened inspection: use of a sampling plan with an acceptance criterion that is tighter than that for the corresponding plan for normal inspection.

NOTE Tightened inspection is invoked when the inspection results of a predetermined number of consecutive lots indicate that the process average might be poorer than the AQL.

Reduced inspection: use of a sampling plan with a sample size that is smaller than that for the corresponding plan for normal inspection and with an acceptance criterion that is comparable to that for the corresponding plan for normal inspection

NOTE 1 The discriminatory ability under reduced inspection is less than under normal inspection.

NOTE 2 Reduced inspection may be invoked when the inspection results of a predetermined number of consecutive lots

🏻GUIDANCE DOCUMENTS AND INFORMATION?

  • 🏻ICH Guidelines : International council on harmonisation guidelines.
  • 🏻WHO Guidelines : World health organization guidelines.
  • 🏻IPEC Guidelines: The international pharmaceutical excipients  council europe.
  • 🏻PIC/S: The pharmaceutical inspection convention and pharmaceutical inspection co-operation scheme.
  • 🏻EMA:  Europe medicines agency European Commission: Medicinal products for human and veterinary use.
  • 🏻PAHO: Pan Americal health organization.
  • 🏻21 CFR Part 210: Current good manufacturing practice in manufacturing, processing, packing, or holding of drugs (General).
  • 🏻21 CFR 211: Current good manufacturing practice in manufacturing, processing, packing, or holding of drugs; Current good manufacturing practice for finished pharmaceuticals.
  • 🏻21 CFR 58: Good laboratory practice for non-clinical laboratory studies.
  • 🏻21 CFR 600 : Biological products in general.
  • 🏻21 CFR 601: Licensing.
  • 🏻21 CFR 610: General biological products standards.
  • 🏻21 CFR 606: CGMP for blood and blood components.
  • 🏻FDA: Food and drug administration.
  • 🏻TGA: Therapeutic goods administraion,Australia
  • 🏻CDSCO: Central drugs standard control orgainzation.
  • 🏻MHRA: Medicine and heath care products regulatory agency.
  • 🏻PMDA: Pharmaceuticals and medical devices agency, Japan.
  • 🏻MEDSAFE: New Zealand medicines

Why Poly Alpha Olefin (PAO) Used in HVAC Validation?

Know more about the Polyalphaolefin (PAO) used in HEPA filter integrity test during HVAC system qualification including their molecular structure. 

Poly Alpha Olefin (PAO) is used for HVAC qualification in pharmaceuticals. PAO is used as a replacement of the DOP (Dioctyl Phthalate) that was used for this purpose from a long time.

Dioctyl 
Phthalate is found as a carcinogen (cause cancer) for human. Scientists were trying to find a material to replace the DOP from a long time. Finally in 2001 Japan Air Cleaning Association (JACA) published a guideline to replace the DOP with PAO. It gives the equal performance to the DOP and doesn’t have any harmful effect on health. FDA also clearly says that alternative aerosols are also acceptable but they should not promote the microbial growth in area. Therefore, it is recommended to replace the DioctylPhthalate with Poly Alpha Olefin (CAS #68649-12-7). The size of PAO generated aerosol ranges from 0.1 to 1.0 μm. The PAO aerosols are generated by aerosol generator and passed through the HEPA filter then the integrity is checked using a photometer. 99.97% particles having size larger than 0.3 μm should not be passed through HEPA filters.

Molecular Structure of Alpha OlefinPoly alpha olefin is a polymer of alpha olefin. Alpha olefin is a class of olefins those have double bond between first and second carbons of the polymer chains. PAO is a mixture of the dimers, trimers and tetramers of the 1-octene, 1-decene and 1-dodecene. Poly alpha olefins have good lubrication properties and greater viscosity than mineral oils. Poly alpha olefins are also used as synthetic lubricants and as a coolant in radiators.

Shelf life of the poly alpha olefin is 10 years in sealed container but for opened container it is one year. It should be protected from UV lightand direct sunlight.