GMP Sub Part - "H" provide valuable information regarding holding and control of pharmaceutical goods, while Sub Part - "I" shows laboratory control and Sub Part - "J" give ideas about record and reports. Very helpful to pharma professionals.

1. By:
Mr. Hardik K. Patel
Lecturer (M. Pharm, MBA)
A. R. College of Pharmacy and
G. H. Patel Institute of Pharmacy,
Vallabh Vidyanagar - 388120
1

2. Subpart – H:
Holding and Distribution
Subpart – I:
Laboratory Controls
Subpart – J:
Records and Reports
2

3. Subpart – H:
Holding and Distribution
3

4. Holding and Distribution (Subpart H):
Written procedures describing the warehousing of
drug products shall be established and followed.
They shall include:
a)Quarantine of drug products before release by the
quality control unit.
b)Storage of drug products under appropriate
conditions of temperature, humidity and light so that
the identity, strength, quality and purity of the drug
products are not affected.
4

5. Traditionally there are two types of warehouse storage
conditions:
1) Ambient conditions:
 For many products an adequate shelf-life can be
determined that encompasses the relatively wide
range of conditions that constitute ‘‘ambient.’’
 Local and national weather records are available
which provide data on temperature ranges.
 Maintenance of actual temperature data in a
warehouse provides the assurance that the
assumptions made in determining shelf-life continue
to be met.
5

6. 2) Refrigerator and freezer:
Certain products that are relatively unstable at
ambient conditions, require storage at lower
temperatures.
Appropriate equipment or areas must be provided
and the conditions monitored to confirm compliance
with the prescribed storage requirements.
6

7. Recently the FDA has begun to insist that all products
should be labeled with defined storage conditions.
One approach used by industry was to declare ‘‘store at
controlled room temperature’’ (15–300
C) with supporting
stability data at 250
C.
A potential problem associated with the declaration of
‘‘controlled room temperature’’ storage is that most
warehouses do not have adequate heating and ventilation
systems to maintain such conditions; on occasion the
temperature may exceed 300
C for short periods.
 However, many companies have now expended the capital
to install air conditioning systems. 7

8. DISTRIBUTION PROCEDURES:
 Written procedures shall be established, and
followed, describing the distribution of drug
products.
 They shall include:
a) A procedure whereby the oldest approved stock of
a drug product is distributed first. Deviation from
this requirement is permitted if such deviation is
temporary and appropriate.
b) A system by which the distribution of each lot of
drug product can be readily determined to facilitate
its recall if necessary. 8

9. Distribution records must be constructed and
procedures established to facilitate recall of
defective product.
A requisite of the system is approval and specific release
of each lot of drug by the quality control function
before distribution can occur.
The manufacturer must maintain records of all
distribution transactions involving in-process or
finished goods.
9

10.  A variety of distribution recording systems may be
utilized. Two of the most commonly used approaches
are:
1) To record the lot or control number on the retained
copies of the shipping invoices
2) To record the dates on which each lot commenced
distribution.
 The distribution process must be arranged so that a
first in/first out movement of product occurs.
 All distribution records should be maintained for a
minimum 3-year period after the distribution process
for any control number has been completed.
 If expiration dating is used for a product, distribution
records must be maintained at least for 1 year past the
expiration date of the product. 10

11. EXAMPLES OF OBSERVATIONS FROM FDA
CITATIONS
1) No procedures available describing distribution of
oldest stock first or any record of batch numbers
entering distribution.
2) Products requiring specific storage conditions, 59–
86°F, were stored in a non-air-conditioned
warehouse at 90°F.
3) No defined quarantine area for incoming finished
drug products to be repacked.
11

12. Subpart – I:
Laboratory Controls
12

13. GENERAL REQUIREMENTS:
a)The establishment of any specifications, standards,
sampling plans, test procedures or other laboratory
control mechanisms required by this subpart, including
any change in such specifications, standards, sampling
plans, test procedures, or other laboratory control
mechanisms, shall be drafted by the appropriate
organizational unit and reviewed and approved by the
quality control unit.
The requirements in this subpart shall be followed and
shall be documented at the time of performance.
 Any deviation from the written specifications,
standards, sampling plans, test procedures, or other
laboratory control mechanisms shall be recorded and
justified.
13

14. b)Laboratory controls shall include the establishment of
scientifically sound and appropriate specifications,
standards, sampling plans, and test procedures designed
to assure that components, drug product containers,
closures, in process materials, labeling and drug
products conform to appropriate standards of identity,
strength, quality and purity.
14

15.  Laboratory controls shall include:
1) Determination of conformance to appropriate
written specifications for the acceptance of each
lot within each shipment of components, drug
product containers, closures, and labeling used in the
manufacture, processing, packing, or holding of drug
products.
 The specifications shall include a description of the
sampling and testing procedures used. Samples
shall be representative and adequately identified.
 Such procedures shall also require appropriate
retesting of any component, drug product container,
or closure that is subject to deterioration. 15

16. 2)Determination of conformance to written
specifications and a description of sampling and
testing procedures for in-process materials. Such
samples shall be representative and properly identified.
3)Determination of conformance to written descriptions
of sampling procedures and appropriate specifications
for drug products. Such samples shall be
representative and properly identified.
16

17. 4)The calibration of instruments, apparatus, gauges,
and recording devices at suitable intervals in
accordance with an established written program
containing specific directions, schedules, limits for
accuracy and precision, and provisions for remedial
action in the event accuracy and/or precision limits are
not met.
Instruments, apparatus, gauges, and recording devices
not meeting established specifications shall not be used.
17

18. TESTING AND RELEASE FOR DISTRIBUTION:
a) For each batch of drug product, there shall be
appropriate laboratory determination of satisfactory
conformance to final specifications for the drug
product, including the identity and strength of each
active ingredient, prior to release.
 Where sterility and/or pyrogen testing are conducted
on specific batches of short-lived
radiopharmaceuticals, such batches may be released
prior to completion of sterility and/or pyrogen testing,
provided such testing is completed as soon as possible.
b) There shall be appropriate laboratory testing, as
necessary, of each batch of drug product required to
be free of objectionable microorganisms. 18

19. c)Any sampling and testing plans shall be described
in written procedures that shall include the method of
sampling and the number of units per batch to be
tested; such written procedure shall be followed.
d)Acceptance criteria for the sampling and testing
conducted by the quality control unit shall be
adequate to assure that batches of drug products meet
each appropriate specification and appropriate
statistical quality control criteria as a condition for their
approval and release. The statistical quality control
criteria shall include appropriate acceptance levels
and/or appropriate rejection levels.
19

20. e)The accuracy, sensitivity, specificity, and
reproducibility of test methods employed by the firm
shall be established and documented.
f) Drug products failing to meet established standards or
specifications and any other relevant quality control criteria
shall be rejected.
 Reprocessing may be performed. Prior to acceptance and
use, reprocessed material must meet appropriate standards,
specifications, and any other relevant criteria.
20

21. STABILITY TESTING:
a) There shall be a written testing program designed
to assess the stability characteristics of drug products.
 The results of such stability testing shall be used in
determining appropriate storage conditions and
expiration dates.
 The written program shall be followed and shall
include:
(1) Sample size and test intervals based on statistical
criteria for each attribute examined to assure valid
estimates of stability.
(2) Storage conditions for samples retained for testing.21

22. (3) Reliable, meaningful and specific test methods.
(4) Testing of the drug product in the same container-
closure system as that in which the drug product is
marketed.
(5) Testing of drug products for reconstitution at the
time of dispensing (as directed in the labeling) as well as
after they are reconstituted.
22

23. b)An adequate number of batches of each drug product
shall be tested to determine an appropriate expiration date
and a record of such data shall be maintained.
Accelerated studies, combined with basic stability
information on the components, drug products, and
container-closure system, may be used to support tentative
expiration dates, provided full shelf life studies are not
available and are being conducted.
Where data from accelerated studies are used to project a
tentative expiration date that is beyond a date supported
by actual shelf life studies, there must be stability studies
conducted, including drug product testing at appropriate
intervals, until the tentative expiration date is verified or the
appropriate expiration date determined.
23

24. c)For homeopathic drug products, the requirements of
this section are as follows:
(1) There shall be a written assessment of stability
based at least on testing or examination of the drug
product for compatibility of the ingredients, and based
on marketing experience with the drug product to
indicate that there is no degradation of the product for
the normal or expected period of use.
(2) Evaluation of stability shall be based on the same
container-closure system in which the drug product
is being marketed. 24

25. d)Allergenic extracts that are labeled ‘‘No U.S. Standard of
Potency’’ are exempt from the requirements of this
section.
The purposes of stability studies are to predict and
confirm product shelf life under the climatic
conditions expected during trade storage, shipping,
house storage and use.
Before commencement of a stability evaluation the
stability protocol should be written and approved
—usually by technical services and QA.
25

26. The key elements of a stability protocol include:
1. Product name and packaging details.
2. Storage conditions.
Various storage conditions included:
Stability storage conditions will normally involve long-
term studies at 250
± 20
C with 60% RH ± 5% with at least 12
months of data before filing
accelerated studies at 400
± 20
C and 75% RH ± 5% with at
least 6 months of data.
26

27. Where ‘‘significant change’’ occurs during the 400
C
accelerated study an additional intermediate station
should be used, such as 300
± 20
C/ 60% RH ± 5%.
‘‘Significant change’’ was defined as a 5% loss of
potency, any degradant exceeding its specification limit,
exceeding pH limits, dissolution failures using 12 units,
failures of physical specifications (hardness, color, etc.).
For less stable products the storage (and labeling)
conditions may be reduced but the accelerated
conditions should still be at least 150
C above those used
for long-term evaluation. 27

28. For products where water loss may be important, such
as liquids or semisolids in plastic containers, it may be
more appropriate to replace the high-RH conditions
by lower RH such as 10–20%.
The same storage conditions are to be applied for the
evaluation of bulk drug substances. However, retest
dates may be used instead of expiration dates.
28

29. 3. Number of batches to be evaluated
Normally a minimum of three batches is required to
provide a sufficient basis for shelf-life prediction.
Development and stability batches may be used
provided they are of the same formulations as the
commercial product and they were processed in an
equivalent manner.
The ICH proposal requires stability data on three
batches, two of which should at least be pilot scale
(not less than 1/10th commercial scale and the same
process or 100,000 tablets or capsules, whichever is
the larger), and the third batch can be smaller.
4. Test methodology. 29

30. 5. Test frequency should be adequate to demonstrate
any degradation and to provide enough data points for
statistical evaluation.
For the scale-up batches and the first three commercial
batches testing is expected initially, at 3 - month
intervals during the first year, 6-monthly in the
second year, and yearly thereafter.
6. Name and/or titles of those responsible for assessing
the data.
30

31. SPECIAL TESTING REQUIREMENTS
a) For each batch of drug product required to be
sterile and/or pyrogen free, there shall be
appropriate laboratory testing to determine
conformance to such requirements.
 The test procedures shall be in writing and shall be
followed.
b) For each batch of ophthalmic ointment, there shall
be appropriate testing to determine conformance to
specifications regarding the presence of foreign
particles and harsh or abrasive substances. The test
procedures shall be in writing and shall be followed.31

32. c)For each batch of controlled release dosage form, there
shall be appropriate laboratory testing to determine
conformance to the specifications for the rate of release of
each active ingredient.
The test procedures shall be in writing and shall be
followed.
32

33. RESERVE SAMPLES:
a) An appropriately identified reserve sample that is
representative of each lot in each shipment of each active
ingredient shall be retained.
 The reserve sample consists of at least twice the
quantity necessary for all tests required to determine
whether the active ingredient meets its established
specifications, except for sterility and pyrogen testing.
 The retention time is as follows:
(1) For an active ingredient in a drug product other than
those described in paragraphs (a) (2) and (3) of this
section, the reserve sample shall be retained for 1 year
after the expiration date of the last lot of the drug
product containing the active ingredient.
33

34. (2) For an active ingredient in a radioactive drug product,
the reserve sample shall be retained for:
(i) Three months after the expiration date of the last lot of
the drug product containing the active ingredient if the
expiration dating period of the drug product is 30 days
or less; or
(ii) Six months after the expiration date of the last lot of
the drug product containing the active ingredient if the
expiration dating period of the drug product is more
than 30 days.
(3) For an active ingredient in an OTC drug product that is
exempt from bearing an expiration date under §211.137, the
reserve sample shall be retained for 3 years after
distribution of the last lot of the drug product containing
the active ingredient. 34

35. (b) An appropriately identified reserve sample that is
representative of each lot or batch of drug product
shall be retained and stored under conditions consistent
with product labeling.
The reserve sample shall be stored in the same
immediate container–closure system in which the
drug product is marketed or in one that has essentially
the same characteristics.
The reserve sample consists of at least twice the
quantity necessary to perform all the required
tests, except those for sterility and pyrogens.
35

36.  The retention time is as follows:
(1) For a drug product other than those described in
paragraphs (b) (2) and (3) of this section, the reserve
sample shall be retained for 1 year after the expiration
date of the drug product.
(2) For a radioactive drug product, the reserve sample shall be
retained for:
 Three months after the expiration date of the drug
product if the expiration dating period of the drug
product is 30 days or less; or
36

37. (ii) Six months after the expiration date of the drug
product if the expiration dating period of the drug
product is more than 30 days.
(3) For an OTC drug product that is exempt for bearing an
expiration date under §211.137, the reserve sample must be
retained for 3 years after the lot or batch of drug
product is distributed.
37

38. Subpart – J: Records and Reports
38

39. Subpart – J: Records and Reports
General Requirements:
(a) Any production, control, or distribution record
that is required to be maintained in compliance with
this part and is specifically associated with a batch of a
drug product shall be retained for at least 1 year after
the expiration date of the batch or, in the case of
certain OTC drug products lacking expiration dating
because they meet the criteria for exemption under
§211.13(expiration dating), 3 years after distribution of
the batch.
39

40. (b) Records shall be maintained for all components,
drug product containers, closures, and labeling for
at least 1 year after expiration date or, in the case of
certain OTC drug products lacking the expiration
dating, 3 years after distribution of the last lot of drug
product incorporating the component or using the
container, closure, or labeling.
(c) All records required under this part, or copies of
such records, shall be readily available for authorized
inspection during the retention period at the
establishment where the activities described in such
records occurred.
These records or copies therefore shall be subject to
photocopying or other means of reproduction as part of
such inspection. 40

41. (d) Records required under this part may be retained
either as original records or as true copies such as
photocopies, microfilm, microfiche, or other accurate
reproductions of the original records.
Where reduction techniques, such as microfilming, are
used, suitable reader and photocopying equipment shall
be readily available.
(e) Written records required by this part shall be
maintained so that data therein can be used for
evaluating, at least annually, the quality standards of
each drug product to determine the need for changes in
drug product specifications or manufacturing or control
procedures. 41

42.  Written procedures shall be established and followed
for such evaluations and shall include provisions for:
1) A review of a representative number of batches,
whether approved or rejected, and, where applicable,
records associated with the batch.
2) A review of complaints, recalls, returned or
salvaged drug products, and investigations
conducted.
42

43. (f) Procedures shall be established to assure that the
responsible officials of the firm, if they are not
personally involved in or immediately aware of such
actions, are notified in writing of any investigations
conducted under §211.198(complaint files),
211.204(returned drug products), or 211.208(drug
product salvaging) of these regulations, any recalls,
reports of inspectional observations issued by the
Food and Drug Administration, or any regulatory
actions relating to good manufacturing practices
brought by the Food and Drug Administration.
43

44. EQUIPMENT CLEANING AND USE LOG
A written record of major equipment cleaning,
maintenance (except routine maintenance such as
lubrication and adjustments), and use shall be included
in individual equipment logs that show the date,
time, product, and lot number of each batch processed.
If equipment is dedicated to manufacture of one
product, then individual equipment logs are not
required, provided that lots or batches of such product
follow in numerical order and are manufactured in
numerical sequence.
44

45. In cases where dedicated equipment is employed, the
records of cleaning, maintenance, and use shall be part
of the batch record.
The persons performing and double-checking the
cleaning and maintenance shall date and sign or
initial the log indicating that the work was performed.
Entries in the log shall be in chronological order.
This section requires written designation of which
equipment is ‘‘major.’’ The intent of the regulations is
not to include small items such as ladles, scoops,
stirrers, and spatulas.
The exclusion of ‘‘nonmajor’’ items from the record
keeping requirement does not, however, exclude them
from the requirements that they be properly cleaned.45

46. As new computerized technology became available it
was possible to move to paperless control of
manufacturing processes.
These computerized controls had several advantages
over manual systems:
More consistent control.
Only approved (trained) personnel could perform a
process.
Processing could be prevented until any prior steps or
checks were performed.
Precise recording of the times of operations were
possible.
Electronic signatures/initials frequently involve a
personal password and a personal magnetic card with a
46

47. COMPONENT, DRUG PRODUCT CONTAINER, CLOSURE
AND LABELING RECORDS:
 These records shall include the following:
a) The identity and quantity of each shipment of
each lot of components, drug product containers,
closures, and labeling,
 the name of the supplier
 the supplier’s lot number(s) if known
 the receiving code
 the date of receipt.
 The name and location of the prime
manufacturer, if different from the supplier, shall be
listed if known. 47

48. b) The results of any test or examination performed
including those performed as required by §211.82(a),
§211.84(d) (testing and approval or rejection of
components, drug product containers and closures) and
the conclusions derived there from.
c) An individual inventory record of each component,
drug product container and closure and, for each
component.
The inventory record shall contain sufficient
information to allow determination of any batch or
lot of drug product associated with the use of each
component, drug product container and closure.
48

49. d) Documentation of the examination and review of
labels and labeling for conformity with established
specifications.
e) The disposition of rejected components, drug product
containers, closure, and labeling.
49

50. MASTER PRODUCTION AND CONTROL RECORDS:
a) To assure uniformity from batch to batch, master
production and control records for each drug
product, including each batch size therefore, shall be
prepared, dated, and signed (full signature,
handwritten) by one person and independently
checked, dated, and signed by a second person.
 The preparation of master production and control
records shall be described in a written procedure
and such written procedure shall be followed.
50

51. b) Master production and control records shall include:
(1) The name and strength of the product and a
description of the dosage form.
(2) The name and weight or measure of each active
ingredient per dosage unit and a statement of the total
weight or measure of any dosage unit.
(3) A complete list of components designed by names
or codes sufficiently specific to indicate any special
quality characteristic. 51

52. (4) An accurate statement of the weight or measure of
each component, using the same weight system (metric,
avoirdupois, or apothecary) for each component.
Reasonable variations may be permitted, however,
in the amount of components necessary for the
preparation in the dosage form, provided they are
justified in the master production and control records.
(5) A statement concerning any calculated excess of
component.
(6) A statement of theoretical weight or measure at
appropriate phases of processing. 52

53. (7) A statement of theoretical yield, including the
maximum and minimum percentages of theoretical
yield beyond which investigation is required.
(8) A description of the drug product containers,
closures, and packaging materials, including a
specimen or copy of each label and all other labeling
signed and dated by the person or persons responsible
for approval of such labeling.
(9) Complete manufacturing and control
instructions, sampling and testing procedures,
specifications, special notations and precautions to be
followed. 53

54. BATCH PRODUCTION AND CONTROL RECORDS:
Batch production and control records shall be
prepared for each batch of drug product produced
and shall include complete information relating to
the production and control of each batch.
These records shall include:
(a) An accurate reproduction of the appropriate
master production or control record, checked for
accuracy, dated, and signed.
54

55. (b) Documentation that each significant step in the
manufacture, processing, packing or holding of the
batch was accomplished, including:
1) Dates
2) Identity of individual major equipment and lines
used
3) Specific identification of each batch of component or
in-process material used
4) Weights and measures of components used in the
course of processing
5) In-process and laboratory control results
6) Inspection of the packaging and labeling area
before and after use
7) A statement of the actual yield and statement of
the percentage of theoretical yield at appropriate
phases of processing
55

56. (8) Complete labeling control records, including
specimens or copies of all labeling used.
(9) Description of drug product containers and
closures.
(10) Any sampling performed.
(11) Identification of the persons performing and
directly supervising or checking each significant step in
the operation.
(12) Any investigation made.
(13) Results of examinations.
56

57. PRODUCTION RECORD REVIEW
All drug product production and control records,
including those for packaging and labeling, shall be
reviewed and approved by the quality control unit to
determine compliance with all established, approved
written procedures before a batch is released or
distributed.
Any unexplained discrepancy (including a
percentage of theoretical yield exceeding the maximum
or minimum percentages established in master
production and control records) or the failure of a
batch or any of its components to meet any of its
specifications shall be thoroughly investigated. 57

58. This section requires that a product be released only
after review of the entire batch record for
compliance with approved written procedures.
That the intent of the section has been shown by the
use of a checklist which defines the specific
documents which should be in the batch record and
what is to be checked on each document.
Items to be entered on the checklists would include:
1. Batch record is current and approved as an accurate
copy.
2. Correct, released, components were used in
manufacturing.
3. Correct quantities of components were used in
manufacturing.
58

59. 4. All components were within the retest dating period.
5. Manufacturing control document is properly
completed.
6. Correct product was packaged.
7. Correct packaging components were used.
8. Labeling bears the correct control number, expiry
date.
9. Yields and accountability are within action levels.
10. Packaging control document was properly
completed.
11. Test and control laboratory data are within
specifications.
12. Retained samples have been taken.
13. Written investigation of any deviation from
procedure, with any approvals and data to support
remedial action. 59

60. LABORATORY RECORDS:
(a) Laboratory records shall include complete data
derived from all tests necessary to assure compliance
with established specifications and standards,
including examinations and assays, as follows:
1) A description of the sample received for testing
with identification of source (that is, location from
where sample was obtained),
 quantity,
 lot number or other distinctive code,
 date on which sample was taken,
 date on which sample was received for testing.
60

61. 2) A statement of each method used in the testing of
the sample.
The statement shall indicate the locations of data that
establish that the methods used in the testing of the
sample meet proper standards of accuracy and
reliability as applied to the product tested.
3) A statement of the weight or measure of sample
used for each test where appropriate.
4) A complete record of all data secured in the course
of each test, including all graphs, charts, and spectra
from laboratory instrumentation properly identified to
show the specific component, drug product container,
closure, in-process material, or drug product, and lot
tested. 61

62. 5) A record of all calculations performed in connection
with the test, including units of measure, conversion
factors, and equivalency factors.
6) A statement of the results of tests and how the
results compare with established standards of
identity, strength, quality, and purity for the
component, drug product container, closure, in-process
material, or drug product tested.
7) The initials or signature of the person who performs
each test and the date (s) the tests were performed.
8) The initials or signature of a second person
showing that the original records have been reviewed
for accuracy, completeness, and compliance with
established standards.
62

63. (b) Complete records shall be maintained of any
modification of an established method employed in
testing.
Records shall include the reason for the
modification.
(c) Complete records shall be maintained of any
testing and standardization of laboratory reference
standards, reagents, and standard solutions.
(d) Complete records shall be maintained of the periodic
calibration of laboratory instruments, apparatus,
gauges, and recording devices.
e) Complete records shall be maintained of all stability
testing performed in accordance with §211.166(stability
testing). 63

64. DISTRIBUTION RECORDS
Distribution records shall contain:
the name and strength of the product,
description of the dosage form,
name and address of the consignee,
date and quantity shipped,
lot or control number of the drug product.
Distribution records include a wide range of
documentation such as invoices, bills of lading, customers’
receipts, and internal warehouse storage and inventory
records..
64

65. COMPLAINT FILES:
a) Written procedures describing the handling of all
written and oral complaints regarding a drug product
shall be established and followed.
 Such procedures shall include provisions for review
by the quality control unit, of any complaint
involving the possible failure of a drug product to
meet any of its specifications and, for such drug
products, a determination as to the need for an
investigation.
 Include provisions for review to determine whether
the complaint represents a serious and
unexpected adverse drug experience which is
required to be reported to the Food and Drug65

66. b) A written record of each complaint shall be
maintained in a file designated for drug product
complaints.
The file regarding such drug product complaints shall
be maintained at the establishment where the drug
product involved was manufactured, processed, or
packed, and are readily available for inspection.
Written records involving a drug product shall be
maintained until at least 1 year after the expiration
date of the drug product, or 1 year after the date
that the complaint was received, whichever is longer.
In the case of certain OTC drug products such written
records shall be maintained for 3 years after
distribution of the drug product. 66

67. 1) The written record shall include :
 the name and strength of the drug product,
 lot number,
 name of complaint,
 reply to complainant.
2) Where an investigation is conducted, the written
record shall include the findings of the
investigation and follow up. The record or copy of
the record of the investigation shall be maintained at
the establishment where the investigation occurred.
3) Where an investigation is not conducted, the written
record shall include the reason that an investigation
was found not to be necessary and the name of the
67

68. Complaints:
Principle:
All quality related complaints, whether received orally
or in writing, should be recorded and investigated
according to a written procedure and corrective actions
should be taken.
Complaints include the following:
Name and address of complainant.
Name (and, where appropriate, title) and phone
number of person submitting the complaint.
Complaint nature (including name and batch number
of the API).
Date on which complaint is received.
68

69. Designation of the person responsible for handling
the complaints
Written procedures describing the action to be taken.
Special attention towards the complaints caused due
to counterfeiting.
Recording of a complaint concerning product defect
with all original details.
Checking of other batches in case of the product
defect is suspected in a batch.
Appropriate follow-up action after investigation and
evaluation of complaints.
Review of the complaints records for any indication
of recurring problems. 69

70. Recording of the measures taken as a result of
complaints.
Informing the competent authority about problems
with a product.
Response provided to the originator of complaint
(including date response sent).
Final decision on intermediate or API batch or lot.
70

71. Records of complaints should be retained in order
to evaluate trends, product-related frequencies, and
severity with a view to taking additional, and if
appropriate, immediate corrective action.
There should be a written procedure that defines the
circumstances under which a recall of an
intermediate or API should be considered.
The recall procedure should designate who should
be involved in evaluating the information, how a recall
should be initiated, who should be informed about the
recall, and how the recalled material should be treated.
71

72. Product recalls:
Principle:
There should be a system to recall the product from
market, promptly and effectively, products known or
suspected to be defective.
Product recall include the following:
Responsibility of an authorized person for
execution and co-ordination of recalls.
Establishments, reviewing and updating of the written
procedures.
Initiation of recall operation promptly in the
distribution chain 72

73. Instruction to store recalled products in a secured
segregated area.
Informing all competent authority to recall a
product.
Availability of distribution records to the authorized
person to permit an effective recall.
Monitoring and recording of progress of the recall
process.
Testing and evaluations of the effectiveness for recall
products. 73

74. REJECTION AND RE-USE OF MATERIALS
Rejection:
Intermediates and APIs failing to meet established
specifications should be identified as such and
quarantined.
These intermediates or APIs can be reprocessed or
reworked. The final disposition of rejected materials
should be recorded.
Reprocessing:
Introducing intermediate or API, one that does not
conform to standards or specifications, back into the
process and reprocessing by repeating a
crystallization step or other appropriate chemical or
physical manipulation steps (e.g., distillation, filtration,
chromatography, milling) that are part of the
manufacturing process is acceptable. 74

75. Continuation of a process step after an in-process
control test has shown that the step is incomplete is
considered to be part of the normal process. This is not
considered to be reprocessing .
Introducing unreacted material back into a process
and repeating a chemical reaction is considered to be
reprocessing unless it is part of the established process.
Such reprocessing should be preceded by careful
evaluation to ensure that the quality of the
intermediate or API is not adversely impacted due
to the potential formation of by-products and over-
reacted materials.
75

76. Reworking
Before a decision is taken to rework batches that do not
conform to established standards or specifications, an
investigation into the reason for non-conformance
should be performed.
Batches that have been reworked should be subjected
to appropriate evaluation, testing, stability testing
if warranted, and documentation to show that the
reworked product is of equivalent quality to that
produced by the original process.
This defines the rework procedure, how it will be
carried out, and the expected results and the batch
released once it is found to be acceptable. 76

77. Procedures should provide for comparing the
impurity profile of each reworked batch against
batches manufactured by the established process.
Where routine analytical methods are inadequate to
characterize the reworked batch, additional methods
should be used.
77

78. Returns
Returned intermediates or APIs should be identified as
such and quarantined.
The returned intermediates or APIs should be
reprocessed, reworked, or destroyed, as appropriate.
Records of returned intermediates or APIs should
be maintained.
For each return, documentation should include:
− Name and address of the consignee
− Intermediate or API, batch number, and quantity
returned
− Reason for return
− Use or disposal of the returned intermediate or API 78

79. 79