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Inspection
Posted on June 12, 2008. Filed under: CGMP | Tags: Inspection, Inspectors, Types of Inspection |

Inspection
Prof. Manohar A. Potdar
Head of Quality Assurance Department, Poona College of Pharmacy, Pune, India
potdar_manohar@yahoo.com.au

Supriya Sharma, Shamita Kohli

Poona College of Pharmacy, Bharati Vidyapeeth University, Pune, India

Inspection means the control and enforces compliance with general Good
Manufacturing Practices or we can say to authorize the manufacture of specific
pharmaceutical products normally in response to a licensing application.
In pharmaceutical field the inspection of manufacturing & Quality Control
facilities are to be done prior to marketing authorization for the product to be granted.
Inspector may be the independent person or a group of person who review the
quality system of a company in compliance with the standards issued by the
International Organization for Standardization (ISO 9000-9004) or British Standards
Institution (BS 5750) with other equivalent National Standards.

Basic requirements for the Inspector:

Inspector should have previous training and practical experience in the manufacture
and Quality Control of pharmaceutical product. Inspector should be graduate
Pharmacist, Chemist or Scientist with an industrial background in pharmaceutical
product. In-post training should include an element of apprenticeship gained by
accompanying experienced inspectors on site visits as well as participation in courses
and seminars on relevant subjects including modern pharmaceutical technology,
microbiology, and the statistical aspects of quality control.

The inspector should have the following attributes:

good knowledge of pharmacy, drugs, and poisons

good knowledge of the laws and regulations to be enforced
 good command of technical terms and excellent communication skills
awareness of the probable methods of using forged or false documents for
transactions in pharmaceutical preparations and skill in determining the
genuineness of documents presented for examination
maturity, honesty and integrity
responsible conduct which commands respect
willingness to accept challenges
ability to organize their own work with minimum supervision
ability to assess facts quickly and take rational and sound decisions without
delay
ability to assess character and honesty of persons being interviewed
good public relations image with key personnel/pharmacists in charge of
premises while remaining firm, fair and resolute
ability to hold discussions with company management at the completion of
inspection
ability to motivate others
commitment to hard work and long hours
ethical approach to any potential conflict of interest.

Inspector’s requirements
Good Inspector
Experience concerning usage and quality problems
Good communication with staff of all levels
Experience of the components manufacturing process
Full understanding of G.M.P. & legal requirements
Familiar with general manufacturing standards operated in industry concerned
Prepare in advance of visit
Realistic prepared to listen

Responsibilities of an Inspector:
An inspector should present a detailed factual report on standards of manufacture and
control applied to specific products. However, inspection should not be limited to
compilation of an inventory of faults, irregularities, and discrepancies. Provided it is in
keeping with national policy and does not breach understandings regarding
confidentiality of information having commercial value, advice may be offered on how
production and control procedures can be usefully upgraded. An inspector should
always be expected, to offer advice on how to improve an in-process test procedure or
to offer other assistance which, in his or her opinion. An inspection should be regarded
as an opportunity to assist and motivate a manufacturer to comply with GMP and to
correct any specific deficiencies.
Types of inspections:

Routine inspection
This is a full inspection of all relevant components of GMP and licensing requirements.
It may be indicated when the manufacturer is newly established or requests the renewal
of a license or he has introduced a new product, or has made a significant
modifications to the manufacturing methods or has made some changes in key
personnel, premises, equipment, etc.;

Concise inspection
Manufacturers with reliable records of compliance with GMP in the course of previous
routine inspections are appropriate for concise inspection. The heart of a concise
inspection is on a partial number of GMP requirements chosen as indicators of overall
GMP recital, with respect to the identification of any noteworthy changes that could
have been introduced since the last inspection. Cooperatively, the information obtained
will indicate the overall attitude of the firm towards GMP. Evidence of unsatisfactory
GMP recital observed throughout a concise inspection should set off a more
comprehensive inspection.

Special inspection
Special inspection are generally carried by visits which may be essential to carry out
spot checks for following complaints or recalls associated to supposed quality defects in
products. Reports of adverse drug reactions may also point out that all is not well. Such
inspections may be focused on one product, a group of related products, or specific
operations such as mixing, sterilization, or labelling. Special visits may also be made to
set up how a specific product is manufactured as a precondition for marketing approval
or issuance of an export certificate. A supplementary reason for special visits is to
congregate specific information on or to investigate specific operations and to advise
the manufacturer of regulatory requirements.

Inspection procedures

The GMP inspectorate should have the necessary resources such as financial, human,
facilities and documented procedures to allow the inspection of manufacturing
operations to be carried out in accordance with the general requirements of the WHO
guidelines on GMP and/or the national GMP guidelines. The GMP inspectorate should
require the manufacturer to have documented procedures in accordance with a quality
management system, and complying with the WHO guidelines on GMP and/or the
national GMP guidelines. The GMP inspectorate should perform regular inspections of
the manufacturing premises, procedures and quality systems of authorization holders at
least once every 2 years in accordance with a written inspection programme. Written
inspection reports should be prepared and sent to the national regulatory authority to
keep it informed of the outcome of such inspections. The arrangement of inspections of
manufacturers and the evaluation of compliance with the planning concerning the
performance of the different types of inspections should be documented. The types of
inspections should include as a minimum routine inspections, specific inspections,
follow-up inspections and concise inspections.

INSPECTION

The activities relating to post-marketing surveillance and product testing should be

described. The description should also cover the process of handling non-conforming
products (e.g. substandard or counterfeit products). The procedure for operations in
support of a surveillance sampling programme should be documented. The GMP
inspectorate should have the documented procedures and resources to enable the
inspection of manufacturing and wholesale distribution operations to be carried out in
accordance with the official guidelines and national legislation. A formal inspection plan
should be followed. All instructions, standards or written procedures, worksheets,
checklists and reference data relevant to the work of the GMP inspectorate should be
kept up to date and be readily available to staff. A chief inspector should be appointed to
coordinate inspection activities if more than one inspector is involved in an inspection.
The lead inspector, who should be selected by all the participating inspectors, should
normally prepare the inspection report. Observations and/or data obtained in the course
of inspections should be recorded in a timely manner to prevent loss of relevant
information. Completed inspections should be reviewed to ensure that the requirements
have been met.

Carrying out the inspection

Emphasis should be positioned on the assessment of the manufacturing procedure,

together with the data verification and the measurement of compliance with GMP. The
production and control procedures described in the application must be compared with
those of used for the make of pre-approval batches. If warranted by records of past
label mix-ups, packaging and labelling control procedures should be evaluated. A
programme of ongoing stability testing needs to be addressed.
The inspection team will determine whether the application provides the scientific data
justifying full-scale production procedures and controls. The validation of pertinent
manufacturing procedures, including equipment qualification, will also be evaluated.
However, inspectors should not suggest withholding endorsement of applications based
on be short of of complete full-scale, multiple-batch validation of sterile and non-sterile
processes, except the data submitted in the application are found to be of doubtful
validity or entirety. It should be understood that full-scale validation may be done after
endorsement of the application, but previous to consignment of the first profitable
batches. Yet, convinced data must be built-in the application to reveal that the
sterilization or aseptic fill procedure has been qualified. The inspection team is
anticipated to audit the data to resolve their genuineness, accuracy and entirety.
Tentative products are frequently produced in facilities other than those used for full-
scale production. These facilities and the related manufacturing and control procedures
are not habitually inspected except validation of the transfer of the methods from the
“investigational” facilities to the full-scale facilities is deficient or doubtful. The facilities
may be periodically inspected when this is required by national legislation/regulation.
Generally inspection is carried out for Quality Management System, Production, Quality
Assurance and Quality Control, Premises and Equipment, Utilities, Safety, Complaints
and Product Recall etc. Basic principles of GMP like Training, documentation,
authorized release, etc should be the main criteria for the inspection.

What the inspector expect and keep in his mind during his inspection according to
W.H.O. and how we can prepare for the same?
There are following things in the mind of inspector. These are classified section wise as
follows: