Lecture 11 cGMP

7/31/2019 Lecture 11 cGMP

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cGMPEleven Lecture


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Intermediate and Bulk Products

1. Intermediate and bulk products should be kept underappropriate conditions

2. Intermediate and bulk products purchased as such should behandled as were starting materials .

Finished Products

1. Finished products should be held in quarantine until their final

release .2. The evaluation of finished products and documentation

necessary for release of a product for sale .


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Rejected and Recovered Materials

1. Rejected materials and products should be clearly marked as

such and stored separately in restricted areas . They should

either returned to the suppliers or reprocessed or destroyed .

2. The reprocessing of the rejected products is permitted only ifthe product quality is not affected i.e. if the product

specification is met .

Recalled Products

Recalled products should be identified and stored separately ina secure area until a decision is taken on their fate .


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Documentation

The documents required are :1. Labels :Labels applied to containers, equipment or premises should be clear and in

companysagreed format . It is helpful in addition to wording on the labels to use colors to

indicatestatus ( quarantined, accepted, rejected, or clean ) .The label for finished product should bearing the following information :a. The name of the drug productb. A list of active ingredients .c. The batch number assigned by the manufacturer .

d. The expiry date in an uncooked form .e. Any special storage conditions or handling precautions that necessaryf. Directions for use, and warnings and precautions that necessary .g. The name and address of the manufacturer or company .


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Specifications and Testing Procedures

1. Testing procedures described in documents should be validated

before they are adopted for testing .

2. There should be appropriately authorized and dated

specifications including : tests on identity , content uniformity ,

purity and quality for staring and packaging materials andfinished products . Also specification for water , solvent , and

reagents used in production .

3. Each specification should be approved and maintained by the

quality control unit .4. Periodic revisions of the specifications may be necessary to

comply with new editions of Pharmacopoeia .


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Specifications for Starting and Packaging materials

Specifications for starting and primary or printedpackaging materials should provide, a description of thematerials including :

a. The designated name and internal code reference .

b. The reference to a pharmacopoeia monograph .c. Qualitative and quantitative requirements with acceptance

limits .d. The supplier and the original producer of the materialse. Directions for sampling and testing .

f. A specimen of the printed materials .g. Storage conditions and precautions .j. The maximum period of storage before re-examination


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Specifications For Finished Products

Specifications for finished products should include :

1. The designated name of the product and the code reference

where applicable .

2. The designated name of the active ingredients .

3. The formula or a reference to the formula .

4. A description of the dosage form and package details .

5. Directions of sampling and testing or a reference to procedure .

6. The qualitative and quantitative requirements with acceptancelimits .

7. The storage conditions and precautions .

8. The shelf-life .


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Master Formulae

A formally authorized master formula should exist for

each product and batch size to be manufactured .

The master formula should include :

1. The name of the product .2. A description of the dosage form, strength and batch size

3. A list of all starting materials to be used with the amount of each .

4. A statement of the expected final yield with the acceptable limits .

5. A statement of the processing location and the principleequipment to be used .


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Master Formulae ( cont..)

6. The methods or the reference to the methods to be used for

preparing the critical equipment e.g. cleaning, assembling,

calibrating and sterilization .

7. Detailed stepwise processing instructions .

8. The instructions for any in-process controls with their limits .

9. The requirements for storage of the products, including the

container, the labeling etc. .10. Any special precautions to be observed .


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Packaging Instructions

Formally authorized packaging instructions should existfor each product, pack size and type . These should

include the following :

1. The name of the product .

2. A description of its pharmaceutical form, its strength and routeof administration .

3. The pack size expressed in terms of the number, weight, orvolume of the product in the final container .

4. A complete list of all packaging materials required for astandard batch size, including quantities, sizes, and types withthe code number relating to the specifications for eachpackaging materials .


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Packaging Instructions ( cont.. )

5. Example of the printed packaging materials indicating where

the batch number and expiry date of the product have been

marked .

6. Special precautions to be observed including examination ofthe packaging area and equipment in order to ascertain the

line clearance before operations begin .

7. A description of the packaging operation and equipment to be

used .8. Details of in-process controls with instructions for sampling and

acceptance limits .


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Batch Processing Records

1. A batch processing record should be kept for each batchprocessed .

2. Before any processing begins a check should be made that theequipment and work station are clear of previous products,documents, or materials not required for the process, and the

equipment is clean and suitable for use . This check should berecorded .

3. During the processing the following information should berecorded at the time each action is taken :

i. The name of the product .

Ii. The number of the batch being manufactured .Iii. Dates and times of the beginning of stages and completion of

production .


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Batch Processing Records ( cont.. )

iv. The name of the person responsible for each stage ofproduction .

v. The initials of the operator of different steps of production andof person who checked each of these operations .

vi. The batch number / control number and the quantity of eachstarting material actually weighed .

vii. Any relevant processing operation and the major equipmentused .

viii. The in-process controls performed, and the results obtained .ix. The the yield of the product with explanations for deviations

from the expected yield .


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Batch Packaging Records

It should be based on the relevant parts of the packaging

instructions . It include the following information :

1. Before any packaging operation begins, checks should be madethat the equipment and workstation are clear .

2. The name of the product, the batch number, and the quantityof bulk product to be packed, as well as the quantity of thefinished product that will be obtained .

3. The date and time of the packaging operations .

4. The name of the responsible person carrying out the packagingoperation .

5. The checks made for identity and conformity with thepackaging instructions including the in-process controls .


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Batch Packaging Records ( cont.. )

6. Details of the packaging operations carried out .

7. Samples of the printed packaging materials used .

8. Notes on any special problems including any deviation from

packaging instructions .

9. The quantities of all printed materials and bulk product issued,used, destroyed, or returned to the stock and the quantities of

the product obtained to permit an adequate reconciliation .


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Standard Operating Procedures ( SOPs)

There should be standard operating procedures and

records for the receipt of each delivery of starting

material and primary and printed packaging material .

The records for the receipts should include :

1. The name of the material on the delivery note and the containers .

2. The in house name / code number of material

3. The date of the receipt

4. The suppliers name and if possible the manufacturers name .5. The manufacturers batch or reference number

6. The total quantity and the number of containers received .

7. Any relevant comment e.g. state of the containers .


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SOP for Sampling

The sampling instructions should include :

1. The method of sampling and the sampling plan .

2. The equipment to be used .

3. Any precautions to be observed to avoid contamination of the

material or any deterioration in its quality .

4. The amounts of sample to be taken .

5. Instructions for any required subdivision of the sample

6. The type of sample containers to be used .7. Any specific precautions to be observed specially in regard to

the sampling of sterile material .


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Good Practices in Production and Quality Control

1. All handling of materials and products should be done in

accordance with written procedures or instructions .

2. Any deviation from instructions should be avoided and if it

occur they should be approved in writing by a designated

person .

3. Checks on yields and reconciliation of quantities should be

carried out to ensure there are no discrepancies outside

acceptable limits .

4. Operations on different products should not be carried out

simultaneously or consecutively in the same room unless is no

risk of mix-up or cross-contamination .


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Good Practices in Production and Quality Control

( cont.. )

5. Access to production premises should be restricted to

authorized personnel .

6. At all the times during processing all materials, bulk containers,

equipment, and rooms used should be labeled that the product

or material being processed , its strength, the batch number

and the stage of production .

7. In-process controls are performed within the production area .


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Prevention of Cross-Contamination and Bacterial

Contamination in Production

Cross-contamination can be avoided by technical or

organizational measures , for example :

1. Production in segregated areas or by campaign followed byappropriate cleaning .

2. Providing appropriate airlocks, pressure differentials, airextraction .

3. Wearing protective clothing in areas where products withspecial risk of cross-contamination are processed

4. Using cleaning procedures of known effectiveness .

5. Using closing system of production .6. Testing for residues .

7. Using cleanliness status labels on equipment .


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Good Practices in Quality Control

Quality control is concerned with :Sampling , Specifications , Testing as well as with

organization, documentation , and release procedures .

Quality control is not confined to laboratory operations,

but must be involved in all decisions that may concern

the quality of the product .

Quality control unit should perform the following :

1. All test procedure for each material or product .

2. Samples should be representative of the batches of material

from which they are taken in accordance with the approved

written procedure .


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Good Practices in Quality Control ( cont.. )

3. Sampling should be carried out so as to avoid contamination orother adverse effects on quality .

4. Sampling equipment should be cleaned before and after each useand stored separately from other laboratory equipment .

5. Each sample container should be a label indicating :a. The name of the sample material .

b. The batch or lot number .

c. The number of container from which the sample has

been taken .d. The signature of the person who has taken the sample .

e. The date of sampling .


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Test Requirements

Before releasing a staring or packaging material for use,the quality control manager should ensure that :

1. The materials have been tested for conformity with

specifications for identity , strength , purity and other

quality parameters .

2. An identity test should be conducted on a sample from each

container of starting materials .

3. Each batch of printed packaging materials must be examined

following receipt .

4. A certificate of analysis may be accepted from supplier,

certificate must be originals, and the certificate must contain

the following information :


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Test Requirements ( cont.. )

4. A certificate of analysis may be accepted from supplier,

certificate must be originals, and the certificate must containthe following information :

1. Identification of the issuing supplier, signature of the manager

or director of QC lab .

2. The name and the batch number of the material tested .

3. A statement of specifications and methods used .

4. A statement of test results obtained and the date of testing .


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Stability Studies

1. The QC unit should evaluate the quality and stability of finishedproducts and when necessary of starting materials andintermediate products .

2. The QC unit should establish expiry dates and shelf-lifespecifications on the basis of stability tests related to storageconditions .

3. A written programmed for ongoing stability determinationshould be developed and implemented to include :


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Stability Studies ( cont.. )

a. A complete description of the drug used in the study .

b. A complete testing parameters and methods for potency, and

physical characteristics .

c. Provision for inclusion of sufficient number of batches

d. The testing schedule for each drug .

e. Provision for special storage conditions .

f. Provision for adequate sample retention .g. A summary of all data generated, including evaluation and the

conclusion of the study .

Documents

Lecture 11 cGMP