Monday, December 30, 2013

Equipment cleaning and use log as per regulatory requirment

CFR - Code of Federal Regulations Title 21

[Code of Federal Regulations]
[Title 21, Volume 4]
[Revised as of April 1, 2013]
[CITE: 21CFR211]


Subpart J--Records and Reports

Sec. 211.182 Equipment cleaning and use log.

Friday, December 6, 2013

A to Z Risk Management with statistical approach

Risk assessment is a systematic examination of a task, job or process that you carry out at work for the purpose of; Identifying the significant hazards that are present (a hazard is something that has the potential to cause someone harm or ill health).
Now a day’s it’s a very popular approach in pharmaceutical industry, Most of the regulatory authority now a day’s looking for risk approach in design to implementation.

ICH guidelines clearly say all the approaches briefly, but the implementation quite difficult practically.
In this article am going to teach you the A to Z of risk in scientific and as well as unscientific


According to the definition, given in Annex 15, 20 of the EU-GMP-Guide and ICH Q9, a risk assessment is a method to assess and characterise the critical parameters in the functionality of an equipment or process. Therefore, risk assessment is a key element in the qualification and validation approach.
In the project context, risk analyses are performed as basic GMP/EHS-Risk assessment, which shall help to identify important GMP/EHS-requirements.

          Aim of the Risk Analysis

At the very basic stage of design the risk assessment is to verify that all features are taken into consideration to avoid the risk of failure of critical GMP and EHS parameter in the equipment.
During study all GMP and EHS parameters will be identified and assessed for the risk if not considered in the design or requirements.
The Risk assessment report is produced to provide the documented evidence that design concepts or requirement are complete in considering all GMP and EHS risks.

RISK Management Process

A typical Risk management process consists of following steps:
·         Risk Assessment:
Ø  Risk Identification
Ø  Risk Analysis
Ø  Risk Evaluation
·         Risk Control
Ø  Risk Reduction
Ø  Risk Acceptance
·         Result of Risk management processes
·    Risk Review

  • Risk Assessment:
It consists of the identification of hazards and the analysis and evaluation of risks associated with exposure to those hazards.

1. Risk identification is a systematic use of information to identify hazards referring to the risk question or problem description.
2. Risk analysis is the estimation of the risk associated with the identified hazards. It is the qualitative or quantitative process of linking the likelihood of occurrence and severity of harm.
3. Risk evaluation compares the identified and analyzed risk against given risk criteria. Risk evaluation considers the strength of evidence for all three of the fundamental questions.
The output of a risk assessment is either a quantitative estimate of risk or a qualitative description of range of risk. In case of qualitative description the risk is expressed using descriptors such as “high”, “medium” or “low”.
  • Risk control:
It includes decision making to reduce and/ or accept risks. The purpose of risk control is to reduce the risk to an acceptable level. The amount of effort used of risk control should be proportional to the significance of the risk.

1. Risk reduction focuses on processes for mitigation or avoidance of quality risk when it exceeds a specified (acceptable) level. Risk reduction might include actions taken to mitigate the severity and probability of harm. 
2. Risk acceptance is a decision to accept risk. Risk acceptance can be a formal decision to accept the residual risk or it can be a passive decision in which residual risks are not specified.
The output/ result of the quality risk management process should be appropriately communicated and documented.

  •  Risk management should be an ongoing part of the quality management process. A mechanism to review or monitor events should be implemented.
The output/ results of the risk management process should be reviewed to take into account new knowledge and experience.

This document applies the risk management principles to identify the risks associated with the design, construction and operational features of any equipment, which is going to be procured and installed in the facility. 
Now a day, its being a practice by pharma major, to adopt the Risk factor before preparing URS of any critical equipment (User Required Specification) and criticality is based on GMP impact assessment. Then all the points are mentioned in URS are addressed through proper risk mitigation method.
Like Loading & Unloading system, Control system, requirement material of construction, alarms, Interlocks & additional safety feature, measurable/calibrated instrument, Documentation for Qualification, Operation & maintenance etc.Different risk tools available as mentioned ICH Q9.

Before going to assessment of any risk we need to work out, what is the severity/impact behind the failure. Second we need to consider probability of occurrence. Risk level depend on the level of these two parameters are enough to assessment primary risk. Qualitative and quantitative both approaches are appreciable.
Risk = Severity (of event occurring) Vs likelihood (of event occurring)

Now tell me how many people working with risk assessment, are you facing difficulties during this??

No need to panic!! Here I am giving the simple solution for Risk assessment.

Problem 1: You have a facility/or hospital/or pharma industry where you looking for best cleaning.

Above mention format is the basic format mostly used by industries.
1. Potential Failure mode : For assessing the probable  failure modes. e.g a. Improper / insufficient sanitization or cleaning
2. Potential effect: Explain what will be the effects for that potential failure. e.g  Increase bio-load in the area/contamination of product and process/area
3. Severity: To assess the impact or how severe it can be . If is take a scale of 1-5 ration, then I will consider as 5 means Severity is high.
4. Contributory factor: Facts that are contributing or probable cause. e.g. Improper disinfectant selection/Frequency of cleaning not established/Untrained stuff/ No written procedure or SOP
6. Occurrence: Assessment of chances or probability of occurrence.
7. Control measures: Area to define the control parameter we are maintaining to minimizing the critical phenomenon. e.g. Select effective disinfectant test for efficacy, if required do 0.2 microne filtration. / frequency need to be validated/ Stuff need to be trained/written procedure to be there where preparation , dilution, frequency and cleaning procedure are defined.
8. detect-ability: If all the measures are taken, then what if the ratio of detection. Rather how easily the risk can be identified.

Saturday, November 16, 2013

Basic design of Air Handling Unit (AHU) Design

There are different sizes and types of Air Handling Units. Some will fit in a closet or within a ceiling space, while others will require a mechanical room or will need to be placed on the roof of a building. Within all of them, however, there is at least one fan and one method of conditioning the air.

These are the basic components in an AHU: Fans, Coils, Filters, Heaters, Humidifiers, Dampers, Mixers, and Enthalpy/Desiccant Wheels. There are other fixtures in an AHU for controls purposes, but basically these are the components you will see on most AHUs.

Saturday, November 9, 2013

Perform Installation Qualification (IQ) in Pharmaceutical Industry

Following qualification study to be perform during Installation qualification but not limited to
·         Training sheet (For keep the training attendance )
·         Purchase order verification (To match with PO)
·         Drawing verification (To verify GA drawing, Electrical drawing etc.)

Wednesday, November 6, 2013

Perform Operation Qualification (OQ) in Pharmaceutical Industry

Following activity shall be performing during the Installation qualification of <Equipment Name> but not limited to.
General test
o   Availability of IQ test report verification
o   Standard operating procedure verification
o   General function test

Guidance to Qualification and Validation towards Global Pharmaceutical Practice

“Documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes.”

The premises, the supporting utilities, the equipment and the processes have been designed in accordance with the requirements of GMP. This normally constitutes Design Qualification or DQ.

Design qualification
The first element of the validation of new facilities, systems or equipment could be design qualification (DQ). Design qualification should provide documented evidence that the design specifications were met.
The premises, the supporting utilities, the equipment and the processes have been designed in accordance with the requirements of GMP. This normally constitutes Design Qualification or DQ. The compliance of the design with GMP should be demonstrated and documented.

Sunday, October 27, 2013

Interview Questions for Pharmaceutical industry related jobs (QA,QC,Production,RA,f&d) for B.pharma /M.pharma (Part 1)

1. What is 21 CFR part  ?

Title 21 CFR Part of the Code of Federal Regulations deals with the Food and Drug Administration (FDA)

2. Different between Qualification and Validation?

“Qualification” refers to the activities performed on facility, utility and equipment
The “Validation” refers to the activities performed on processes, practices and methods.

Tuesday, October 1, 2013

Air Changes Calculations in clean rooms

Step 1: Measure the length, width and height of the room using a good old fashioned tape measure :-) This will determine the size of the room or in other words its volume.

Length x Width x Height =
Step 2: Using a device called a ‘balometer’ measure the air supply coming out of the HEPA terminal. You do this by holding the balometer up to the HEPA terminal. The balometer will catch the downstream of air flowing into the cleanrooms and measures the cascade speed.
 Step 3: Once you have your cascade speed your next step is to multiply this figure by 3,600 and divide by the room volume.
 3,600 = Number of seconds per hour
Remember to round up to 1 decimal point on your final answer!

Sunday, September 29, 2013

What is 100 Class (Grade A) area ?

A cleanroom or clean room is an environment, typically used in manufacturing or scientific research that has a low level of environmental pollutants such as dust, airborne microbes, aerosol particles and chemical vapors. More accurately, a clean-room has a controlled level of contamination that is specified by the number of particles per cubic meter at a specified particle size.

Saturday, September 28, 2013

Interview Questions for Pharmaceutical industry related jobs (QA,QC,Production,RA,f&d) for B.pharma /M.pharma (Part 2)

      Interview questions for Technician (engineer) in parenteral injectable plant   
      1.  Which test should to be perform for detect the leakage & penetration of steam in Steam sterilizer/ Autoclave?
Answer: The identification for any leakage & penetration of steam can be tested by the following methods: Chamber Leak Test, Bowie Dick test
     2.      Mention the name of all the utility required to run the steam sterilizer/ Autoclave.
      Answer: Plant Steam for Jacket, Pure Steam for Chamber, Soften Water for Vacuum System, Compressed Air

Sunday, August 4, 2013

Interview Questions for Pharmaceutical industry related jobs (QA,QC,Production,RA,f&d) for B.pharma /M.pharma (Part 3)

  • Interview Questions for Quality Assurance (QA- Validation) in pharmaceutical industry

    Final round of Interview questions in technical round (Sun Pharmaceutical Industries Ltd.)

    1. What is the recommended bio burden limits of purified water & WFI?

    Purified water has a recommended bioburden limit of 100 CFU/mL, and Water for injection (WFI) has a recommended bio burden limit of 10 CFU/100 mL.

    2.  What is the standard number of rotations used for friability test?

          100 rotations

    3. What is the fall height of the tablets in the friabilator during friability testing? 

         6 inches.Tablets falls from 6 inches eight in each turn within the apparatus.

Tuesday, May 28, 2013

Interview Questions for Pharmaceutical industry related jobs (QA,QC,Production,RA,f&d) for B.pharma /M.pharma (Part 4)

  • Interview Questions for Production (Injectable preparation) in pharmaceutical industry

    Final round of Interview questions in technical round in Production (SPV) :

    1. Principle of Autoclave operation. 
    2. Basics of cleaning validation during change over of different product in filling. 
    3. How to take swab from filling needle in filling machine ?
    4. Handling of filters and filter integrity test
    5. Steps of media fill protocol.
    6. About Viable and non viable monitoring in clean room. 

Tuesday, May 21, 2013

Interview Questions for Pharmaceutical industry related jobs (QA,QC,Production,RA,f&d) for B.pharma /M.pharma (Part 5)

  • Interview Questions for Production (Injectable preparation) in pharmaceutical industry (Cipla)

    Final round of Interview questions in technical round in Parenteral Production (SPV) :

    1. Viable and non viable limits for classified area. 
    2. Acceptable Lux value as per guidelines for visual inspection of filled vials or ampoule.
    3. Endotoxin, Bioburden, TOC Limits of WFI comparison to Purify water.
    4. Material use in class B clean room garment.
    5. Calculate log reduction in Depyrogenic Tunnel , temperature mapping in Tunnel
    6. Operation of vial/ampoule washing machine.
    7. IPQA checks in parenteral formulation.   

Tuesday, April 23, 2013

Guidelines for viable & non -viable counts in gmp areas (As per WHO,2011)

Manufacture of sterile pharmaceutical preparations, four grades of clean areas are distinguished as follows:
  • Grade A: The local zone for high-risk operations, e.g. filling and making aseptic connections. Normally such conditions are achieved by using a unidirectional airflow workstation. Unidirectional air flow systems should provide a homogeneous air speed of 0.36–0.54 m/s (guidance value) at a defined test position 15–30 cm below the terminal filter or air distributor system. The velocity at working level should not be less than 0.36 m/s. The uniformity and effectiveness of the unidirectional air flow should be demonstrated by undertaking airflow visualization tests.
  • Grade B: In aseptic preparation and filling, this is the background environment for the Grade A zone.
  • Grades C and D: Clean areas for carrying out less critical stages in the manufacture of sterile products or carrying out activities during which the product is not directly exposed (i.e. aseptic connection with aseptic connectors and operations in a closed system).

Tuesday, March 19, 2013

Review - Quality control of parenteral products

In a pharmaceutical organization a quality control deals with testing, sampling, specification, and documentation, release procedure which ensure that all tests are actually carried out prior to release of material for sale or use. Four basic area of testing parenteral are Sterility, Freedom form Pyrogens, Freedom from particulate matter and leakers. The achievement of sterile, non pyrogenic and particulate free parenteral product provides a significant challenge to ingenuity and creativity of parenteral scientist and technologist.

Friday, January 18, 2013

Distinguish between dissolution and disintegration

Disintegration time is the time required for a dosage form to break up in to granules of specified size (or smaller) under carefully specified conditions.

Where as dissolution is a process by which solid substance enters in the solvent to yield a solution.It is controlled by the affinity between the solid substance and the solvent.

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