What are the contents of Annual product quality review (APQR)?

Contents of an APQR is:

1.       Introduction

2.       Number of Intermediates and APIs batches produced

3.       Review of output for all Isolated Intermediates and Finished Products

4.       Review of Critical Quality attributes of In-process, Isolated Intermediates and Finished Products

5.       Summary of changes made during the year with respect to equipment, Process, Specifications, and Methods, Raw materials and others.

6.       List of Deviations and a brief description of deviations and action taken.

7.        List of customer complaints; Return goods and Recalled goods along with description and actions are taken.

8.       Number of Reprocessed and Reworks batches in all stages during the year-2009

9.        Review of Key starting materials and Primary packing materials and Rejections.

10.   Review of Bioburden on the product (for a minimum of 3 batches)

11.   Review on Stability studies and Summary

12.    List of Out of specifications for Finished products

13.   Review of Retained samples quality (Finished product)

14.   Review of Validation packages (Process, Equipment, Procedure)

15.   Status of Drug Master File (if any), Drug Master File new updates

16.    Details of special training provided to employees in case of Deviations or Complaints received regarding a particular product

17.   Summary Report

What are the different types of safety factors used in the pharmaceutical industries?

Following safety factors are used in pharmaceutical manufacturing.

•  1/10 to 1/100th of a normal daily dose = Topical products

•  1/100 to 1/1000th of a normal daily dose =     Oral products

• 1/1000 to 1/10000th of a normal daily dose = Injectable & Ophthalmic products

• 1/10000 to 1/100000th of a normal daily dose = Research, investigational products.

What is the solubility data as per any Pharmacopoeia?

Different products have different solubility levels. The solubility of the product is determined by dissolving in know volume of solvent.

•  Approximately volume of solvent in ml per gram of solute at 20° to 30°C
• Very soluble : Less than 1
• Freely soluble : From 1 to 10
• Soluble : From 10 to 30
• Sparingly soluble : From 30 to 100
•  Slightly soluble : From 100 to 1000
•  Very slightly soluble : From 1000 to 10000
• Insoluble / practically soluble : More than 10000

 Example:  Very soluble means one gram of solute substance will require less than 1 ml of solvent.

What is the necessity of analytical method validation?

The principle purpose of analytical validation is to ensure that a selected analytical procedure will give reproducible and reliable results that are adequate for the intended purpose. It is thus necessary to define properly both the conditions in which the procedure is to be used & the purpose for which it is intended.

 It means that analytical method validation is to prove that the analytical method used for analysis of the product works perfectly.

Define Bio burden?

The level & type (i.e. objectionable or not) of microorganisms that can be present in raw materials, API starting materials, intermediates or APIs. Bioburden should not be considered contamination unless the levels have been exceeded or defined objectionable organisms have been detected.

 It means the bioburden is the number microbes present in the raw material or water sample. Bioburden does not claim any specific microorganism.

Describe the method of testing for checking of MOC of SS material (Molybdenum test)?

Procedure:

1.   Put one drop of the electrolyte solution of molybdenum test kit on the clean metal surface, which is to be tested.

2.       Switch on the detector and touch the metal tip of the detector on the metal surface & carbon point in the electrolyte solution.

3.       Do not pass the current for more than 3 to 4 seconds.

4.       If the red color appears and is stable for more than 2 seconds then it can be concluded that MOC of the part being tested is SS-316.

5.       If the solution remains colorless or green color appears then it can be concluded that MOC of the part being tested is SS-304.

6.       If the black color appears & is stable for more than 2 seconds then it can be concluded that MOC of the part being tested is SS-302.

What are the test parameters in the nitrogen gas validation?

Test parameters during validation and its frequency are given below:

a) Test for oil mists - Every 6 months once

 b) Test for moisture content - Every 6 months once

c) Particulate count (Non-viable) - Every 6 months once

d) Sterility test (Aseptic area locations) - Every 6 months once

e) Bioburden test (Controlled area locations) - Every 6 months once

The purity of nitrogen gas (Based on manufacturer COA)

 * Perform the nitrogen gas sampling & testing for three consecutive days.

What do you mean by Critical Quality Attributes?

A critical quality attributes is a physical, chemical, biological or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality.

It defines that critical quality attribute is to maintain the product quality within the predefined limits.

What are the possible reasons for the Non-conformities?

Non-conformities are the deviations from the predefined standards. Generally, these are findings in a requlatory audit.

 The following are the possible reasons, but not limited:

·         Management attitude

·         Ineffective documentation

·         Lack of trained personnel

·         Lack of co-ordination/ co-operation within or among departments.

What are the types of DMF?

Drug master files are regulatory submission requirements.

There are four types of DMF. They are referred to by their numbers in Roman numerals:

Type-I: Is an obsolete number once used for a category that no longer exists because it was found to easily fit into and overlap with the other four categories.

 Type-II: DMF is for companies who supply drug substances, drug products, intermediates & material used in their manufacture.

Type-III: DMF is for companies who supply packaging (container closure system) for human drugs & biologics.

Type-IV: DMF is for companies who supply excipients

Type-V: DMF is for companies who supply clinical services, sterile manufacturing etc.

What is a DMF?

A Drug Master File (DMF) is a submission to the Food and Drug Administration (FDA) that may be used to provide confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs.

A DMF is a package of proprietary information filed voluntarily by a company with the FDA. If it held by them in confidential closed files until such time as an FDA reviewer requests a review of the DMF.

What are the different climate zones in the world?

Different zones of the world have different climatic conditions. The world is divided into the five climate zones and is given :

Zone	Name	Conditions
I	Temperate	21° C / 45% RH
II	Subtropical & Mediterranean	25° C / 60% RH
III	Hot & Dry	30° C / 35% RH
IV A	Hot & Humid	30° C / 65% RH
VB	Hot & Very Humid	30° C / 75% RH

What are the advantages of Rinse sampling?

Rinse samples are taken during the cleaning of the equipment. A large surface area of the equipment can be sampled using this technique.

Following are some advantages of rinse sampling.

• ·         Adaptable to online monitoring
• ·         Easy to sample
• ·          Non-intrusive
• ·          Less technique dependent that swab
• ·         Applicable for active, cleaning agents & excipients allow sampling of large surfaces
• ·         Allows sampling of unique (e.g. porous) surface.

What are the advantages of Swab sampling?

Swab samples are taken from equipment as well as other areas. It is useful to take a sample of sticky material.

 Following are some advantages of this sampling technique.

• ·         Dissolves & physically removes a sample
• ·         Adaptable to a wide variety of surfaces
• ·         Economical & widely available
• ·         May allow sampling of a defined area
• ·         Applicable to active, microbial & cleaning agent residues.

What is commissioning?

Commissioning is an engineering term that covers all aspects of bringing a system /sub-system to a position where it is regarded as being ready for use in pharmaceutical manufacture. Commissioning involves all the basic requirements of Installation qualification (IQ) & Operational Qualification (OQ).

In simple words, commissioning is the process to start a system from its initial stage to the working stage where the system is ready to work.

What is the difference between controlled copy and un-controlled copy?

Controlled copy: A controlled copy is a formal copy of the latest, correct issue of a document; an identified issue of a document to an individual or location of the record. The controlled copy is officially tracked, updated & destroyed to assure that it is current.

Uncontrolled copy: An informal copy of a document for which no attempt is made to update if after distribution; the document is marked “uncontrolled” and the user determines if the document is active prior to use. Controlled and uncontrolled copies of the documents are issued by the quality assurance department as per the official requirements. Uncontrolled copies are unofficial copies of documents generally, issued for review purpose.

What do you mean by re-validation?

A repeat of the process validation to provide an assurance that changes in the process/ equipment introduced in accordance with change control procedures do not adversely affect process characteristics & product quality.

 Revalidation is to validate any process or equipment again after the maintenance or change that can affect the quality of the product. It ensures that the system or equipment is working as per the standards.

What are the possible causes for “Out of Specification”?

 Out of specification is the deviation of the product from the pre-determined specification.

The following are the possible causes for out of specification:

• ·         Test analysis error in QC Lab.
• ·          Lab equipment malfunctioning or off-calibrated
• ·         Production equipment malfunctioning or off-calibrated
• ·         Operator/human errors

What is the difference between specification and Limit?

Specification: A document giving a description of a starting material, packaging material, intermediate, bulk or finished product in terms of its chemical, physical & possibly biological characteristics. A specification normally includes description clauses & numerical clauses, the latter stating standards & permitted tolerances.

Or

 It is the type of standard which is often referenced by a contract or procurement document. It provides the necessary details about the specific requirements.

 Or

 Lists of detailed requirements with which the products/ materials used or obtained during manufacture have to conform. They serve as a basis for quality evaluation.

Limit: The point, edge or line beyond which something cannot or may not be proceeding. The boundary surrounding a specific area, bounds.

Describe about swab and rinse sampling?