Charge in of components

1. Presented By:-
Machhi Dhruvi Anilkumar
1st Sem. M.Pharm.
Department of Pharmaceutical Quality Assurance
Smt. B. N. B. Swaminarayan Pharmacy College, Salvav-vapi
Topic:- Charge in of Components
Course Name:- Quality Control & Quality Assurance
Course Code:- MQA103T
1
Guided By:-
Miss. Priya Shukla
Assistant Professor
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Dhruvi Machhi Smt.BNB.SPC,Salvav-Vapi

2. Charge in of components:
It is a CFR rule 211.101.
Written production and control procedures shall include the
following, which are designed to assure that the drug
products produced have the identity, strength, quality, and
purity they purport or are represented to possess:
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3. (a) The batch shall be formulated with the intent to provide not
less than 100 percent of the labeled or established amount of
active ingredient.
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4. (b) Components for drug product manufacturing shall be
weighed, measured, or subdivided as appropriate.
If a component is removed from the original container to
another, the new container shall be identified with the
following information:
1. Component name or item code;
2. Receiving or control number;
3. Weight or measure in new container;
4. Batch for which component was dispensed, including its
product name, strength, and lot number.
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5. (c) Weighing, measuring, or subdividing operations for
components shall be adequately supervised.
Each container of component dispensed to manufacturing shall
be examined by a second person to assure that:
1. The component was released by the quality control unit;
2. The weight or measure is correct as stated in the batch
production records;
3. The containers are properly identified. If the weighing,
measuring, or subdividing operations are performed by
automated equipment under § 211.68, only one person is
needed to assure paragraphs (c)(1), (c)(2), and (c)(3) of this
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6. (d) Each component shall either be added to the batch by one
person and verified by a second person or, if the components
are added by automated equipment under § 211.68, only
verified by one person.
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 The requirement to ‘‘formulate with the intent to provide not less than 100% . . . of the
active ingredient’’ requires some explanation.
 This certainly makes it unacceptable to add only sufficient material to meet the lower end
of the specification, although no reputable manufacturer would ever use this approach.
 It is not the intention of the regulations to require calculation of an exact amount of active
ingredient based on the assay value of the material for each batch of product.
 Most active ingredients show assay results that are not exactly 100%. With inherent errors
in analytical methodology in the order of 1–2% it is not possible to precisely determine the
‘‘true’’ assay value.
 Consequently it is acceptable to use material that is within the acceptable specification
without specific adjustment to accommodate batch analytical variations.
 This may not be adequate for materials with a significant, and variable, loss on drying.
 When it is necessary to calculate a specific quantity this requirement should be specified in
writing by QC and not be the subject of telephone or other verbal communication.
 For a product that is known to show some inherent loss of potency during the production
process, it may be advisable to take the assay value into account for each batch. It may also
be necessary to add an overage to allow for this potency loss.

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 The dispensing step is a critical stage of the manufacturing operation.
 It ensures that the right amounts of the correct material, released by QC, are
allocated to the specified batch of product.
 The labeling of the component containers ((b)(1)–(4)) makes the later checking at
production usage more effective.
 As written, §211.101(b) could be interpreted that it is only necessary to include the
labeling requirements if material is transferred from its original container.
However, such a literal interpretation would be illogical and would weaken the
system since the original container will not reference the drug product name,
strength, or lot number.
 The dispensing operation also provides an ideal opportunity to visually examine
containers for damage, and contents for atypical appearance or foreign matter.
 Dispensing operators should be made aware of the importance of this role to the
achievement of quality standards.

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 The requirement that ‘‘each container of component dispensed to manufacturing shall be examined by a second
person’’ (§211.101(c)) is usually interpreted to mean that a second person should be available in the dispensary to
perform this duplicate check.
 Several alternatives would also appear to achieve the same result.
 A single check could be performed in the dispensary with the second check being done on receipt by production.
 With some manual systems the dispensary label can be removed at the production stage and become part of the
batch record.
 Either routinely, or in the event of a problem, the individual labels can be examined.
 A second effective alternative is the replacement of the second check by the availability of a suitable computer
system.
 Computer systems are available that will prevent the weighing of an incorrect or unreleased component; they will
also disallow completion of the dispensing step if the amount of material being weighed is outside of the defined
operational tolerances.
 Such systems can also be designed to allow only designated individuals to weigh out specified materials, as in the
case of controlled substances or materials to which an individual employee may be allergic.
 Another alternative is the use of bar codes, applied to the incoming materials, and the monitoring of their use and
disposition throughout the production operation by scanning equipment.
 These systems provide much more effective control over the dispensing function than does a second human check
and should be introduced whenever possible.
 An added advantage of such systems is that they allow immediate reconciliation; in the event that a raw material
being weighed did not correlate with the records, the dispensing could be automatically put on hold until an
investigation had been initiated.

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 The requirement for a second person, in production, to verify the addition of
components to a process is subject to the same argument as that used above for
dispensing.
 For example, if component containers are provided with a bar code, the scanning
of this bar code on addition to the batch would provide the assurance required.
 The overall topic of double-checking has been raised by industry with the FDA.
 As indicated above, the alternative approaches are much more effective and
provide a higher level of assurance that specific actions have been performed.
 This is an excellent illustration of the CGMP regulation being too detailed and too
restrictive.
 Unfortunately, the alternative approaches are not acceptable to the FDA without a
change in the regulations—which tends to take a considerable time.

11. Reference:
1. Title 21--food And Drugs, Chapter I--food And Drug Administration, Department Of Health
And Human Services, Subchapter C - Drugs: General, Part 211 -- Current Good
Manufacturing Practice For Finished Pharmaceuticals, Subpart F - Production And Process
Controls, Sec. 211.101 Charge-in of components.
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=211.101
2. Sharp, John. "Good manufacturing practices for pharmaceuticals: a plan for total quality
control from manufacturer to consumer (revised and enlarged), Sidney H. Willig, Marcel
Dekker Inc.,5e, New York, ISBN 0-203-90876-7", 2001: 105-107.
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