The document outlines the regulatory requirements for quality reviews in pharmaceutical manufacturing, detailing the distinctions between FDA's Product Annual Review (PAR) and European Union's Product Quality Review (PQR). It emphasizes the importance of compliance with Good Manufacturing Practices (GMP) and outlines necessary documentation, inspections, and error handling processes. Additionally, it highlights the need for training, thorough review meetings, and timely follow-up actions to ensure product quality and safety.

1. 1
PREPARED BY:AJAY KUMAR

2.  Q.R are planned and documented by an inspections of
a review item
 The review item may be a product, a group of related
products or a part of a product
 If the error identified earlier the cost of implication is
less and the penality for failing to conduct adequate
reviews
2

3.  The US FDA proposed the requirement in Feb.13,
1976 rewriting of the GMP’s
 The purpose was to provide reliable procedure for a
drug manufacturer to review the quality standard
 Completeness
 Compliance with Instruction/directives
3

4.  Q.R requirement was published in Sep. 1978 for drug
product (21 CFR 211.180(e)) and became effective on
march 28, 1979(1)
 Since Q.R publication, 21 CFR 211.180(e) has been
commonly referred to by FDA and the pharmaceutical
industry as the “Product Annual Review" (PAR) or the “
Annual Product Review"(APR)
 Check your own work
4

5. The 3 required FDA objectives are:
1. Manufacturing process
2. Manufacturing controls and
3. Product specification
5

6.  EU PQR required objectives are:
1. Product specification
2. Identification of improvement
3. High lightening trends
4. Appropriateness of starting material
requirement specifications
6

7.  Conduct annually
 Extension of time may leads to “
potential problems”
7

8.  Investigating Officer training- formal training by
the inspector-invesigation requirements- -Judge
advocate participation
 Planning- where do you want to go?. Brainstorm
with inspector- Identify the documents need-
prepare witness list-prepare questions
 Witness Interviews-Interview complaint list-outline
of questions-follow up procedure requirement
8

9. The FDA PAR specifies - 6 items
 The EU PQR Specifies – 19 items
 The Q7A PQR specifies – 11 items
9

10. Four of the six requirement common to both the
EU PQR and Q7A PQR are:
1. Complaints
2. Product recalls
3. Returned product
4. Investigation
10

11. 1. Export only products
2. Marketing authorization variation
3. Post marketing
4. Equipment qualification status
5. Effectiveness of preventive actions
6. Adequacy of previous product process or
equipment corrective actions
11
Other EU PQR requirements are:

12.  Review for all batches that failed specifications
 Critical deviation and non-conformities
 Product stability results
 Critical in process controls and test results
 Changes in analytical methods
 Effectiveness of corrective action
12
EU PQR AND Q7A PQR REQUIREMENTS:

13.  FDA revised its GMP in Jan 1995 to review
representative number of batches.
 Representative batch –as a batch that are
- Released, rejected or recalled
- Subject of FDA field alert
- With manufacturing discrepancies
- In need for change
13

14.  EU requirement – emphasis on license
- emphasis on drug safety
 During inspection – question the firm management
about their knowledge and assurance of commitment
14

15.  Agreement between MAH (Marketing authorization
holder) and the manufacturer
 Analysis-process must be fully documented with
evidence- how it is resolved with credible witness-why
the documentary evidence was important?
 Findings-Unfounded-not substantiated-substantiated-
each one separately addressed
 Documentary evidence-Plan in advance- all
documentary evidence must be included
 Comments/ tones- No personnel attack, relevant
comments only
 Timely communication of results
15

16.  Equipment qualification
 Equipment requalification
 Preventive maintenance and calibration programs
as per FDA’s 1987 validation guidelines
 Modular approach-divide in to smaller parts
16

17.  Quality system approach to pharmaceutical CGMP
regulation have parallels in the EU PQR(7)
 Elements such as system review,
 Examination of inputs ( raw materials ),
 Process improvements,
 Data evaluation activities and addressing discrepancies
are common to both the modern quality system described
by the FDA guidance and the EU PQR
17
:

18. :
 It is the responsibility of the chairman and presenter to
organize the Q.R and notify all reviewers invited
 Invitation and copies of the products being reviewed
should be issued, allowing sufficient time for each
reviewer to compile an error list
 In this phase reviewers should check the product for
defects or omissions' using the product descriptions and
review checklists
18
.

19.  Error list and copies of annotated products should be
brought to the meeting by each reviewers
 During the review meeting the emphasis should be
on error detection, in line with the criteria, and only
limited discussion of corrective action should occur
19
:

20.  It is important that 'personalities' and 'politics' are kept
out of the review
 For reviews that are ' complete' the action list tasks are
allocated along with designated reviewers, to verify that
the work is done
 A project exception report should be raised for any
errors detected in non review items
20

21.  Follow up period during which the errors identified at
the review that were committed to follow up action list
are rectified and signed off
 At the end of the follow up period ' which is typically
restricted to one week, the follow up action list should
be signed off by the chairman
21

22.  Quality review studies indicate that the product is within
the specified limits
 Q.R reviews all documents to be sure there are no
loose ends and also examines testing data to confirm
that the product meets specifications
 If there is significant problem with the product, GMP’s
require the Q.C group to reject the product and
investigate
22
:

23.  http://www.fda.gov/cder/guidance/index.
htm.
 http://api.ning.com.
23

24. 24