qa apl u – xiitraining division 1 code of federal regulations parts 210 and 211 module – iii,...

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Code of Federal Regulations

Parts 210 and 211Module – III, Section - 1

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•21 CFR Part 210

Current Good Manufacturing Practice in Manufacturing, Processing, Packing or Holding of Drugs; General.

•21 CFR Part 211

Current Good Manufacturing Practice for finished Pharmaceuticals

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Pa rt 210 Pa rt 211


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PART 210 – CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PROCESSING,

PACKAGING OR HOLDING OF DRUGS; GENERAL

Section210.1 Status of current good

manufacturing practice regulations.210.2 Applicability of current good manufacturing practice regulations.210.3 Definitions

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Status of current good manufacturing practice regulations

• Regulations of the section give about minimum cGMP’s for all manufacturing operations.

• Failure to comply with these minimum requirements 210 through 226 shall render the product adulterated and the personnel involved in such manufacturing operations shall be subject to regulatory action.

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Applicability of cGMP regulations

Regulations of parts 210 through 226 – applicable to drug.

Regulations of parts 600 through 680 – applicable to biological product for human use.

No documents or regulations mentioned here shall supercede each other, they shall be supplemented.

Personnel engaged in the operations subject to these regulations partially need to comply to those partial operations only.

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Definitions

Act, Batch, Component, Drug, Fiber, Non- Fiber- releasing

filter, Active ingredients, Inactive ingredients, In-Process material,

Lot, Lot number, Strength, Quality, Control, Theoretical yield, Actual yield, Acceptance criteria, Representative

samplesetc. are defined

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• Batch: A specific quantity of a drug or other material that is intended to have uniform character and quality, within specified limits, and is produced according to a single manufacturing order during the same cycle of manufacture.

• Component: Any ingredient intended for use in the manufacture of a drug product, including those that may not appear in such product.

• Drug: A finished dosage form, for example, tablet, capsule, solution etc. that contains an active ingredient generally, but not necessarily, in association with inactive ingredients.

• Fiber: any particulate contaminant with length at least three times greater than its width.

• Non Fiber Releasing filter: any filter which after an appropriate pretreatment such as washing or flushing, will not release the fibers into the component or the drug product that is being filtered.

• Active ingredient: Any component that is intended to furnish pharmacologically activity or other direct effect in the diagnosis, cure, mitigation, treatment or prevention of any disease, or to affect any structure or any function of the body of man or animals.

• In-Process material means any material fabricated, compounded, blended or derived by chemical reaction that is produced for, and used in the preparation of the drug product.

• Lot or Batch: Specific identified portion of a batch, having uniform character and quality within specified limits, In case of a drug product produced continuous process, it is a specific identified amount produced in a unit of time or quantity in a manner that assures its having uniform character and quality within specified limits.

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Strength: The concentration of the drug substance (for example,

weight/weight, weight/Volume,e, or unit dose/volume basis of time or quantity in a manner that assures its having uniform character and quality within specified limits.

The potency that is the therapeutic activity of the drug product as indicated by appropriate laboratory tests or by adequately developed and controlled clinical data(expressed, for example, in terms of units by reference to a standard).

Theoretical Yield: The quantity that would be produced at any appropriate phase of manufacture, processing, or packaging of a particular drug product, based upon the quantity of components to be used, in the absence of any loss or error in actual practice.

Actual Yield: The quantity that is actually produced at any appropriate phase of manufacture, processing or packing of a particular drug product.

Acceptance Criteria: the product specifications and acceptance/rejections criteria, such as acceptable quality level unacceptable quality level, with an associated sampling plan, that are necessary for making a decision to accept or reject a lot or a batch.

Representative sample: A sample that consists of a number of units that are drawn based on the rational criteria such as random sampling and intended to assure that the sample accurately portrays the material being sampled.

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Holding & Distribution

Organisation & Personnel

Buildings & Facilities

General

Packing & Labelling Con.

Pro. & Pro Controls

Control of Component.

Equipment

Production

Returned & Salvaged Drugs

Records & Reports

Laboratory Controls

QA & QC

CFR-PART 211cGMP for Finished Products

Flow chart for Training program on CFR 211

Scope & Definition

Holding & Distribution

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Subpart ILaboratory Controls

Subpart GPackaging & Labelling Controls

Subpart EControl of Components & Drug Product

Containers & Closures

Subpart CBuildings & Facilities

Subpart AGeneral Provisions

Subpart KReturned & Salvaged Drug Products

Subpart JRecords & Reports

Subpart HHolding & Distribution

Subpart FProduction & Process Controls

Subpart DEquipment

Subpart BOrganisation & Personnel

Part 211cGMP for Finished Products

PART 211 – CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS

General

Production

QA QC

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Subpart ILaboratory Controls

Subpart GPackaging & Labelling Controls

Subpart EControl of Components & Drug Product

Containers & Closures

Subpart CBuildings & Facilities

Subpart AGeneral Provisions

Subpart KReturned & Salvaged Drug Products

Subpart JRecords & Reports

Subpart HHolding & Distribution

Subpart FProduction & Process Controls

Subpart DEquipment

Subpart BOrganisation & Personnel

Part 211cGMP for Finished Products

PART 211 – CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS

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PART 211Sub Part A – GENERAL PROVISIONS

211.1 Scope:

a) Regulations in this part contain those minimum cGMP’s for preparation of drug products and biologicals for administration of humans or animals.

b) cGMP regulations in this part pertain to drug products and in parts 600 through 680 pertain to biologicals intended for human use.

c) Requirements may not be met for OTC drug products when those and their ingredients are marketed and consumed as human food.

211.3 Definitions: Same definitions given under CFR 210 are applicable to this section

too.

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211.22 Responsibilities of Quality Control Unit.

a) A Quality Control Unit shall be responsible for authorizing of various materials in several stages along with their documents.If any errors were observed they should be investigated fully.

b) Adequate lab facilities for testing approval or rejection of components shall be available.

c) QC shall Approve or Reject the materials after testing as per procedures.

d) All responsibilities and procedures applicable to QC shall be written down and they shall be followed.

PART 211Sub Part B – ORGANISATION & PERSONNEL

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211.25 Personnel Qualification

a) There shall be adequate number of trained, experienced and qualified people for supervising the manufacturing operations.

b) All personnel involved in the manufacturing and its ancillary services shall be literate, qualified, experienced and trained.

c) All personnel shall protect themselves and the products integrity by following the GMP’s

211.28 Personnel Responsibilities

a) Personnel shall wear clean clothing appropriate for their duties who were engaged in manufacturing operations.

b) Personnel shall practice good sanitation and health habits.

c) Authorization shall be given to Personnel along with limited access to buildings and facilities.

d) Any person with illness shall be excluded from all those operations which deal with direct product contact.

PART 211Sub Part B – ORGANISATION & PERSONNEL

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211.34 Consultants Consultants advising on the manufacturing operations shall be highly

qualified and experienced. A record shall be maintained stating complete detail of the consultants.

Reject the materials after testing as per procedures.

What does UK MCA say about Organisation and personnel

PART 211Sub Part B – ORGANISATION & PERSONNEL Contd.

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211.42 Design & Construction features

a) Buildings used in the manufacturing operations shall be suitably constructed to facilitate maintenance and cleaning.

b) Buildings shall be provided with adequate place and equipment shall be placed orderly. Adequate space shall be provided for proper storage of materials in various stages.

c) All operations shall be performed within specifically defined areas of adequate size. All the areas and process flow should be such that it prevents the contamination and mix ups during course of following operations.

PART 211Sub Part C – BUILDINGS & FACILITIES

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211.42 Contd.

1) Receipt, identification, storage and withholding from use of components, drug product containers, closures and labeling, pending the appropriate sampling, testing, or examination by the quality control unit before release for manufacture.

2) Holding rejected components, drug product containers, closures and labeling before disposition.

3) Storage of released components, drug product containers, closures and labeling.

4) Storage or In-process materials.

5) Manufacturing and processing operations.

6) Packaging and labeling operations.

7) Quarantine storage before release of drug products.

8) Storage of drug products after release.

9) Control and laboratory operations.

10) Aseptic processing, which includes as appropriate


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211.42 Contd.

i. Floors, walls and ceilings of smooth, hard surfaces that are easily cleanable.

ii. Temperature and humidity control.

iii. Proper Air Handling Systems, HEPA filters and LAF’s.

iv. System of monitoring environmental conditions.

v. Systems for cleaning and disinfecting rooms and equipment.

vi. System for maintaining any equipment used to control aseptic conditions.

d) Any operations involving manufacture of penicillin shall be performed in separate facilities.

211.44 Lighting Adequate


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211.46 Ventilation, Air Filtration, Air Heating & Cooling

a) Adequate ventilation shall be provided.

b) Adequate control over air pressure, temperature, humidity, dust etc.

c) Air filtration systems shall be used when appropriate at defined areas.

d) AHU systems for penicillin's shall be completely separate.

211.48 Plumbing

a) Plumbing system free of defects shall be used to supply potable water under positive pressure continuously. Potable water shall meet the standards set by Environmental Protection Agency’s Primary Drinking Water Regulations set forth in 40 CFR part 141.

b) A proper drainage system shall also be provided.


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211.50 Sewage and Refuse Sewage, Trash and other refuse from the buildings and immediate

premises from the building shall be disposed safely.

211.52 Washing and Toilet Facilities Adequate washing facilities shall be provided (includes Hot, cold

water, Detergent or Soap solution, Air Dryers).

211.56 Sanitation

a) Buildings used in manufacturing operations shall be maintained in clean and sanitary condition.

b) There shall be written down procedures assigning responsibilities for sanitation, cleaning schedules, procedures etc.

c) Good sanitation facilities , along with written down procedures for Sanitation, Pest Control & Cleaning etc. shall be maintained.

d) Sanitation procedures shall apply to all workers and employees in the premises.


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211.58 Maintenance Proper maintenance shall be provided to all buildings involved in

manufacturing operations

What does UK MCA say about Premises and Equipment


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211.142 Warehousing procedures There shall be written procedures for warehousing of drugs.

a) Quarantine of drug products before release by quality control unit.

b) Storage of drug products under controlled conditions shall be followed to preserve the identity, strength, quality and purity of the drug.

211.150 Distribution Procedures There shall be written procedures for Distribution of drugs. They shall

include

a) Oldest approved drug product shall be distributed first.

b) Distribution records of each drug product shall help in tracking the movement of the drug product and easy recalls when needed.

PART 211Sub Part H – HOLDING AND DISTRIBUTION

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Flow chart for training program on MCA Guidelines

T ra in ing Program on G uide l ines of M C A (O range G uide )

Prem ises & Equipm ent

Personnel

G enera l

M anufacture ofSterile M edicinal

Products

Production

Production

Self Inspection

Com plaints &Product recall

Contract M anufacture& Analysis

Quality Control

Docum entation

QualityM anagem ent

Q A & Q C

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PERSONNEL

MAINTENANCE OF A SATISFACTORY QA SYSTEM AND QUALITY PRODUCTS RELIES UPON.

People

Training

Personnel Hygiene

PREMISES AND EQUIPMENT.

Premises

Equipments

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PERSONNEL

PEOPLE.

Manufacturing has the responsibility to provide sufficient Qualification personnel for carrying out various tasks.

Individual responsibilities must be clearly understood by the individual

All personnel must be aware of GMP’s / GLP’s

All personnel must receive initial and containing training, including hygiene instructions

The responsibilities placed on any one individual should not be extensive as to present any risk to quality.

The manufacturer must have an organisation char. People in responsible should have specific duties, written job description and adequate authority.

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PERSONNEL

PEOPLE.

Key posts should be occupies by full time personnel.

Heads of production and QC must be independent from each other.

TRAINING.

The manufacturer should provide training for all the personnel, whose activities should effect the quality of the product..

New recruits should receive training appropriate to the duties assigned to them.

Training should be ongoing and its effectiveness periodically assessed.

Training records should be kept

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PERSONNEL

TRAINING

Training programs should be available and approved by QC or production head, as appropriate.

Visitors or untrained personnel should be given information in advance on hygiene and protective clothing. They should be closely supervised.

PERSONNEL HYGIENE

Hygiene programs should include procedures related to the health, hygiene practices and clothing. The Procedures should be understood and practiced strictly.

All personnel should receive medical examinations on recruitment and thereafter periodically.

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PERSONNEL

PERSONNEL HYGIENE

Steps must be taken to ensure that no person affected by infectious diseases or having open cuts on exposed surfaces of body is engaged in the manufacturing process.

Every person entering manufacturing areas should wear protective garments, appropriate to the operations to be carried out.

Direct contact between operator's hands and the exposed product or m/c contact parts should be avoided.

Personnel should be instructed to use hand washing facilities.

Continue with CFR

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PREMISES AND EQUIPMENTS

PREMISES

Premises should be situated in an environment which presents minimal risk of contamination.

Premises should be carefully maintained, ensuring that repair or maintenance so not present any hazard to product quality.

Lighting, temperature, humidity and ventilation should be appropriate.

Premises should be designed and equipped so as to afford maximum protection against the entire of insects, rodents or other animals.

Entry to production, storage and CC areas should be restricted to authorized people only.

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PREMISES

Dedicated and self contained facilities to avoid cross contamination e.g., penicillin's, biological preparation, hormones, cytotoxics, nonmedicinal products, highly potent drugs etc..

In exceptional cases, principle of campaign working in the facility can be accepted, provided that specific precautions are taken and necessary validations are made.

Poisons, pesticides, herbicides not allowed in premises, used for medicinal products.

Premises should be laid so as to allow production in a logical order.

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PREMISES

In process storage space should permit orderly and logical positioning of materials.

Where starting and primary packaging materials, intermediates, bulk products are exposed, the walls floors and ceiling should be smooth, free from cracks, crevices, open joints etc.

Concealed fittings to avoid the creation of recesses which are difficult to clean.

Drain points must be designed to avoid back flow.

Production areas should be effectively ventilation with air control facilities, (including temperature and where necessary, humidity and filtration) appropriate booth to products handled and operations undertaken.

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PREMISES

Weighing of stating materials usually should be carried out in a separate weighing room, designed for that use..

Where powder dust is generated, specific provisions should be taken on ensure dust containment.

Packaging area must be designed to avoid mix-ups or cross contamination.

Production areas should be well lit, particularly where visual on line control are carried out.

Storage areas should be sufficient capacity to allow orderly storage of RM’s, PM’s, intermediates, bulk and finished products.

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PREMISES

Storage area should be designed to ensure good storage conditions and maintained within acceptable temperature limits, where required, temperature and humidity controls must be provided, which need to be checked and monitored.

Receiving and dispatch bays should protect goods from weather. Receiving areas should be designed and equipped to allow cleaning of oncoming materials, before storage.

Physical quarantine or any system which should give equivalent security. Restricted to authorized parsons only.

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PREMISES

Separate sampling area preferable. If performed in storage area, all precautions to be taken t prevent contamination / cross contamination.

Segregate areas for the storage of rejected, recalled or returned goods.

Safe and secure storage of printed packaging materials.

QC laboratory should be separated form production areas.

QC laboratory should be separated from production areas.

Control laboratories should be designed to suit the operations to be carried out in them. There should be adequate storage space for samples and records.

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PREMISES

Separate rooms to protect sensitive instruments.

Rest and refreshment areas should be separate from other areas

Facilities for changing cloth, hand /foot wash and toilets.

Toilets should not directly open to production or storage areas.

Maintenance workshops should be separate from production areas.

Animal house must be well isolated form other areas.

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EQUIPMENTS

Designed to suit intended purpose and offer easy cleaning as per written procedure.

Contact parts of the equipment must not be reactive, additive or absorptive.

Contact parts of the equipments must not be reactive, additive or absorptive.

Measuring, weighing recording and control equipment should be calibrated and checked at defined intervals and record maintained.

Fixed pipe work should be labeled with flow direction.

Water system should be sanitized at defined intervals as per written procedures.

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EQUIPMENTS

Defective equipments should be removed or labeled as defective.

Continue with CFR

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211.63 Equipment design, size and Location All equipment shall be of appropriate design, adequate size & suitably

located.They shall provide ease of maintenance.

211.65 Equipment Construction

a) Material of construction of all equipments shall not be reactive, additive, absorptive.

b) Lubricants & Coolants shall not come in contact with the product.

211.67 Equipment cleaning & maintenance

a) Equipment and utensils shall be cleaned, maintained and sanitized at appropriate intervals.

PART 211Sub Part D – Equipment

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b) Written down procedures shall be established for cleaning and maintenance of the equipment and other utensils used in manufacturing operations. These procedures shall include, but are not necessarily limited to,

1) Assigning responsibilities for cleaning.

2) Maintenance and cleaning schedules along with sanitization schedules.

3) Description of methods, materials to be used to clean equipment.

4) Removal of previous batch identifications if any.

5) Protection of cleaned equipment from contamination.

6) Inspection of equipment and area cleanliness.

c) Record maintenance for cleaning sanitization operations and schedules.


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211.68 Automatic, mechanical and electronic equipment

a) Any automatic, mechanical or electronic instruments used in the manufacturing process including computers shall be checked and calibrated at regular intervals and the results documented.

b) Appropriate controls and personnel shall be authorised over computer related systems to avoid changes in master records and control records.

211.72 Filters Non-Fiber-releasing filters shall be used in filtration processes.

( especially for liquid dosage form manufacturing units)


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211.80 General requirements

a) Written down procedures shall exist for Receipt, Identification, Storage, Handling, Sampling, testing, approval and rejection of materials.

b) Storage of the component containers and closure shall prevent contamination.

c) Storage of bagged or boxed containers should suffice cleaning of floor.

d) Distinctive code number shall be given for separate containers having different Lot numbers, each lot shall be identified appropriately as to its status.( Quarantined, approved or rejected).

PART 211Sub Part E – Control of Components & Drugs product Containers and Closures

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211.82 Receipt, Storage of untested components, drug product, containers and closures.

a) All received materials shall be physically examined for appropriate labeling, container damage or broken seals and contamination.

b) Materials shall be quarantined as per standard procedures till they are examined and approved.

211.84 Testing, approval or rejection of components, drug products, containers and closures.

a) Lot shall be withheld in quarantine till the material is approved.

b) Representative sample of each shipment of each lot shall be collected for testing and examination.Sampling shall be done as per the standard procedures( No. of containers to be sampled, amount of material to be taken etc).


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c) Sampling shall be done as per the standard procedures.

1) Containers of components selected shall be cleaned.

2) Opened containers shall be resealed securely to prevent contamination.

3) Sterile equipment and aseptic sampling shall be followed where ever necessary.

4) Containers shall be sampled from top, bottom and middle.

5) Sample containers shall be properly labeled.

6) Containers from which were taken shall be marked.

d) Samples shall be examined and tested as follows.

1) Atleast one test for identity of each component of drug product, specific identity tests if any.

2) Each component shall be tested for conformity with written specifications for purity, strength and quality.


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3) Each component shall be tested for conformity with written specifications for purity, strength and quality. A certificate of testing may be obtained from the manufacturer.

4) When appropriate components shall be examined microscopically.

5) Established specifications and storage conditions shall be followed for those drugs products and their closures which are prone to contamination by filth and insects.

6) Those container and products prone to microbial contamination shall be checked with specific microbial tests.

e) Tests done on the lot if prove the product to be as per specification only then shall the products be used or else they shall be rejected.


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211.86 Use of Approved components, drug product containers and closures.

Oldest Approved stock shall be used first. Deviation from this requirement shall be permitted only if it is appropriate and temporary.

211.87 Retesting of approved components, drug products, containers and closures.

Retesting shall be done on the materials as per the appropriate procedures for their identity, strength, quality and purity. This shall be done after storage for long periods or after exposure to air, heat or any other conditions which may adversely effect the drug quality.

211.89 Rejected components, drug product containers and closures. A proper identification, control and quarantine system shall exist for

rejected materials.


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211.94 Drug product containers and closures.

a) Drug product containers shall be clean shall provide adequate protection to and shall remain inert towards the drug.

b) Drug product containers shall provide adequate protection against external foreseeable external factors.

c) Containers shall be clean and they shall be sterilized and depyrogenated where ever applicable.

d) Standards or specifications, methods of cleaning and sterilizing etc shall be followed on the drug product containers where ever applicable.


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211.100 Written Procedures; Deviations

a) Written down procedures for production and process controls shall exist to produce a quality product once and always. Any changes in such procedures shall be drafted, reviewed and approved by appropriate organizational units.

b) Written procedures shall be followed for all production process and any deviations shall be recorded and justified.

211.101 Charge – in of Components Written procedures for production and process controls shall include

the following.

1) Batch formulation is done with an intent to provide 100 % of the label claim of the active ingredient.

a) All components for drug product manufacturing shall be weighed, measured or subdivided appropriately. If components are taken from new containers they shall be identified with following information.

PART 211Sub Part F – Production and Process Controls

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b) All components for drug product manufacturing shall be weighed, measured or subdivided appropriately. If components are taken from new containers they shall be identified with following information.

1) Component name, item code.

2) Receiving or control number.

3) Weight or measure in new container.

4) Batch for which the component was dispensed including the product name, strength and lot number.

c) Weighing and measuring or subdividing operations for components shall be adequately supervised.

1) The component was released by the quality control unit.

2) The weight or measure is correct as stated in BPR,

3) Each component shall be added to the batch by one person and shall be verified by the second.


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211.103 Calculation of Yield Actual yield and percentage of theoretical yield shall be calculated

after every operation and recorded.

211.105 Equipment identification

a) All compounding and Storage containers, processing lines other equipment used in production operation shall be identified properly. To indicate their contents, phase of processing of batch.

b) A distinctive identification code number shall be assigned to all major equipment. This helps in precise identification of the specific equipment used in the manufacturing process while noted in the Batch Production Record.


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211.110 Sampling and testing of in-process materials and drug products.

a) To assure batch uniformity and integrity of the drug products written procedures shall be established. Such control procedures of in-process materials help in monitoring the output and validating the performance of the processes. Such controls shall include but are not limited to the following.

1) Tablet or capsule weight.

2) Disintegration time

3) Adequacy of mixing (time)

4) Dissolution time and rate,

5) Clarity, pH of solutions etc.

b) All such inprocess specifications shall be derived from previous acceptable process average and process variability estimates.

c) In-process materials shall be tested for identity, quality, purity and strength during the production process, after short or long breaks in process.


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d) A system shall be followed where in the rejected materials shall be identified, quarantined and prevented from usage in manufacturing operations.

211.111 Time limitations on Production. If any time limits are framed for different stages in manufacturing of

the batch, deviation from the time limits shall be recorded and justified. The deviations are acceptable only if they do not pose damage to the quality of the drug product.

211.113 Control of microbial contamination.

a) Written procedures designed to prevent objectionable micro organisms in drug products shall be followed. Such procedures shall be properly validated.


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211.115 Reprocessing

a) Written procedures shall be established for reprocessing of the batches to ensure the established standards, specifications and characteristics.

b) Reprocessing shall be performed only with review and approval of quality control unit.


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211.122 Materials examination and usage criteria

a) Written down procedures shall exist. Labeling and packaging materials shall be representatively sampled, examined and tested.

b) Only approved labeling and packing materials shall be used. Unapproved materials shall be rejected.

c) Records shall be maintained of all the received shipments indicating receipt, examination or testing and whether accepted or rejected.

d) Different product labels shall be stored separately with suitable identity. Access to the storage area shall be limited.

e) Obsolete and out dated labels and other packaging materials shall be destroyed.

f) Use of gang printed labeling for different drug products, or different strengths or net contents of same drug product, is prohibited unless labeling from gang-printed sheets is adequately differentiated by size, shape and colour.

PART 211Sub Part G – Packaging and labeling Controls

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g) If cut labeling is use packing and labeling operations shall include following procedures

1) Dedication of labeling and packing lines to each different strength of each different drug product.

2) Use of electronic equipment to conduct a 100% examination for correct labeling.

3) Use of visual inspection to check proper labeling, such operations shall be done by one person and supervised by another.

h) Printing devices and equipment in the manufacturing lines shall be monitored.


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211.125 Labeling Issuance

a) Strict control shall exist on issuance of labels.

b) Careful examination for identity and conformity to labels specified in the MFR/ BPRR shall be done.

c) Reconciliation procedures shall exist for quantities of labeling materials used, returned etc.

d) All excess labels shall be destroyed.

e) Returned labels shall be maintained and stored to prevent mix ups and provide proper identity.

f) Written controlled procedures for issuance of labeling material shall exist.

211.130 Packing and labeling Operations

a) Procedures for preventing mix ups and contaminations,

b) Identification and handling of filled drug product containers that are set aside and held.


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c) Identification of drug product with lot number or control number.

d) Examination of packing and labeling materials before using for the suitability and correctness.

e) Inspection of the packing and labeling facilities before use to assure that the area is clean from products of previous batch.

211.132 Tamper-Resistant packing requirements for the Over – the – Counter (OTC) human drugs.

a) General. The FDA has authority to establish a uniform requirement for tamper resistant packaging of OTC drug products. Any OTC drug product that is not packed, or properly labeled is considered to be adulterated or misbranded.

211.134 Drug product inspection.

a) Packaged and labeled products shall be examined during finishing operations to provide assurance and correctness of labeling.

b) Representative sample of units shall be retained.

c) Results of these examinations shall be recorded in BPR or control records.


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211.137 Expiration Dating

a) To assure that the drug product meets applicable standards of identity, quality, strength and purity appropriate stability testing shall be done.

b) Expiration dating shall be related to any storage conditions stated on the label as determined by stability studies.

c) If the drug product is to be reconstituted expiration dating shall be given to both un reconstituted drug and reconstituted solution.

d) Expiration dating shall be as per the requirements.

e) Homeopathic drug products shall be exempted from these requirements.

f) Allergenic extracts that are labeled “no U.S Standard of potency” are exempted from these requirements.

g) New drug products for investigational use shall be exempted when they meet appropriate standards and specifications as demonstrated by stability studies data.

What Does ORANGE GUIDE tell about Production Aspects.


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4.5.1 GENERAL Production should be performed & supervised by competent people. Production activities from receipt of materials to packing & distribution

should be done in accordance with written procedures & recorded. Any damage to raw material containers should be investigated, recorded &

reported. All incoming materials should be checked to ensure that the consignment

corresponds to the order. Incoming materials and finished product materials should be quarantined

until release or use for distribution. Materials & products should be stored as per the manufacturers instruction. Checks on yields & reconciliation on quantities should be carried out. Operations on different products should not be carried out simultaneously or

consecutively in the same room, unless there is no risk of mix ups or cross contamination.

UK MCA4.5. PRODUCTION

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General contd.. At every stage of processing, microbial or other contamination should be

avoided. Power dust should be contained during processing. Equipments shall be clearly labeled to indicate the product, strength, stage

batch number etc. Use different colour labels to indicate status. If deviation occurs it should be approved in writing by a competent person

with the involvement of QC. Access to production premises should be restricted to authorised personnel.

UK MCAPRODUCTION

62QA APL U – XII

Training Division

4.5.2. PREVENTION OF CROSS CONTAMINATION IN PRODUCTION.

Contamination and cross contamination shall be avoided. Using dedicated areas Providing air locks Avoiding re-circulation of air Laying emphasis on clothing & gowning Using closed systems of production Testing for residues, after cleaning.

4.5.3. VALIDATION Carry out validations in accordance to defined procedures. New manufacturing formula should be shown to yield a product

consistently of the required quality Amendments to the manufacturing process or change in equipment or

materials should be validated. Process & procedures should undergo periodic revalidation.

UK MCAPRODUCTION

63QA APL U – XII

Training Division

4.5.4. STARTING MATERIALS Starting materials should be purchased only from approved vendors. Containers of starting materials shall be checked for integrity of packing and

seal. If one material delivery is made up of different batches, each batch must be

considered as separate for sampling, testing and release. Labels on the containers of the starting materials should indicate

o Name of product

o Code number

o Batch number

o Status

o Expiry date

o Retest date Released starting materials should be used. Dispensing of the starting materials should only be done designated person as

per written down procedures.

UK MCAPRODUCTION

64QA APL U – XII

Training Division

Starting Materials Contd.. Dispensed materials & their weights/volumes should be independently

checked & recorded. Materials dispensed for each batch shall be kept together and labeled.

4.5.4. PROCESSING OPERATIONS INTERMEDIATE AND BULK PRODUCTS

Before starting any processing operations, line clearance must be taken. Inprocess controls & environmental controls should be carried out &

recorded. Any significant deviation from the .only be done designated person as per

written down procedures.

UK MCAPRODUCTION

65QA APL U – XII

Training Division

4.5.5. PACKING MATERIALS

Printed packaging materials should be stored in secured condition.

Cut labels and loose printed materials should be transported in separate close containers.

Only authorised persons should issue the packaging materials.

Each delivery or batch of materials should be given a specific reference number.

Out dated or obsolete materials should be destroyed & recorded.

UK MCAPRODUCTION

66QA APL U – XII

Training Division

4.5.6. PACKING OPERATIONS

Different products should not be packaged in close proximity unless there is physical segregation.

Before any packaging operation, line clearance should be taken as per the check list.

Name & batch number of the product being packed should be displayed at each packing line.

Containers for filling should be cleaned before filling.

Filling & sealing should be immediately followed by labeling.

Special care should be taken when using cut labels. Roll feed labels are preferable to cut labels.

In-house printing on packaging materials must be resistant to fading or erasing.

Online inprocess controls on packing lines are to be carried out.

UK MCAPRODUCTION

67QA APL U – XII

Training Division

4.5.6. PACKING OPERATIONS contd.

Final re-conciliation of the product & printed packaging material should carried out. Any deviation should be investigated and recorded.

Upon completion of packing operation, unused batch coded printed packaging materials should be destroyed & recorded.

Documented procedure should be followed if un-coded printed materials are returned to the stock.

4.5.7. FINISHED PRODUCTS

Finished products should be held in quarantine until release.

UK MCAPRODUCTION

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Training Division

4.5.8. REJECTED, RECOVERED AND RETURNED MATERIALS

Rejected materials should be stored separately in a restricted area.

Reprocessing of rejected products should only be permitted if the quality of the final product is not affected. Reprocessing report should be kept.

Addition of recoverable residues into fresh batch of the products should be authorised & carried out in accordance with a defined procedure.

Returned goods should be destroyed unless there is no doubt that their quality is satisfactory. The decision lies with QC.

UK MCAPRODUCTION

End Session

69QA APL U – XII

Training Division

211.160 General requirement:

a) The establishment of any specifications, standards, sampling plans, test procedures or other laboratory control mechanisms required by this subpart, including any change in specifications, standards, sampling plans, test procedures or other laboratory controls 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.

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

PART 211Sub Part I – Laboratory Controls

70QA APL U – XII

Training Division

211.160 General requirement:

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 the drug products. Samples shall be representatives and adequately identified.

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

3) 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 precision limits are not met, instruments, apparatus, gauges and recording devices not meeting established specifications shall not be used.


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Training Division

211.165 Testing & Release for Distribution:

a) For each batch or drug product, there shall be appropriate laboratory laboratory determination of satisfactory conformance to final specification for the drug product including identity the identity and strength of each active ingredient prior to release.

b) There shall be appropriate laboratory testing, as necessary, of each batch of the drug product required to be free of objectionable microorganisms.

c) Any sampling and testing plans shall be described in written procedure 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 the batches of drug products meet each appropriate specification and appropriate statistical quality control criteria as a condition for their approval and release.

e) The accuracy, sensitivity, specificity and reproducibility of test methods employed by the firm shall be established and documented.


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Training Division

211.166 Stability testing:

a) There shall be a written testing program designed to asses the stability characteristics of the drug products. The results of such testing shall be used to determine the storage conditions and expiration dates. The written program shall be followed and includes.

1. Sample size and test intervals based on statistical criteria for each attribute examined to assure valid estimate of stability;

2. Storage conditions for samples retained for testing;

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 the drug products for reconstitution at the time of dispensing(as directed on the labeling) as well as after they are reconstituted.

b) An adequate number of batches of each drug shall be tested to determine an appropriate expiration date and record of such datd shall be maintained.


73QA APL U – XII

Training Division

211.166 Stability testing:

b) Accelerated stability studies along with the basic stability data on the components and the 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 the data from the 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 the drug product testing at appropriate intervals, until the tentative expiration date is verified or the appropriate expiration date is determined.

c) For homeopathic drug products, the requirements are as follows.

1. Written assessments of stability data, of the drug product compatibility with other ingredients shall exist. The data proving that no degradation of the drug has occurred in normal period of use shall also be provided.

2. Container-closure system compatibility with the drug and its stability data shall exist.

3. Allergenic extracts that are labeled :No U.S. standard of potency are exempted.


74QA APL U – XII

Training Division

211.167 Special Testing Requirements:

a) Each batch of product purporting to be sterile or pyrogen free shall have a specific laboratory test procedure and it shall be documented.

b) Ophthalmic ointments shall have specific documented test procedures showing their conformance with the foreign particles, harsh or abrasive substances.

c) For controlled release dosages, written test procedures determining the rate of release of the drug product shall exist.

211.170 Reserve Samples:

a) An appropriately identified reserve sample shall be retained that represents a specific lot. The reserve samples contain at least twice 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:


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Training Division


1. For an active ingredient in a drug product other than those described in paragraphs (a) (2) and (3) of this section, the reserve samples shall be retained for 1 year after the expiration date of the last lot of the drug product containing the active ingredient.

2. For an active ingredient in a radioactive drug product, except for nonradioactive reagent kits, the reserve samples 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.

iii. 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 the distribution of the last lot of the drug product containing active ingredient.


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Training Division


b) The reserve samples shall be stored under the conditions consistent with product labeling. The samples shall be stored in the same container closure system. Reserve samples shall be at least twice the quantity to perform all the tests. Reserve samples shall be examined visually at least once a year for evidence of deterioration unless the visual examination would affect the integrity of the reserve sample. Any evidence of the deterioration of the reserve samples shall be recorded and shall be maintained with other stability data on the drug product. Reserve samples of compressed gases need not be maintained.

211.173 Laboratory Animals:

Animals used in testing components, inprocess material, or drug products for compliance with the established specifications shall be maintained and controlled in a manner that assures their suitability for their intended use. They shall be identified adequate records shall be maintained showing the history of their use.


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Training Division

211.176 Penicillin Contamination:

Lot/ batch of drug products suspected for penicillin contamination shall be vigorously tested. Penicillin levels shall be detected as per the procedures for Detecting and Measuring the penicillin contamination in drugs.


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Training Division

211.180 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 shall be retained for at least 1 year after the expiration date of the batch.

b) Records shall be maintained for all components, drug product containers, closures and labeling for at least 1` year after the expiration date.

c) All records required under this part, or copies of such records shall be readily available for authorized inspections during the retention period at the establishment where the activities described in such records occurred.records that can be immediately retrieved from another location by computer or other electronic means shall be considered as meeting the requirements of this paragraph.

PART 211Sub Part J – Records and Reports

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Training Division


d) Records under this part shall be retained as original records or as true copies such as photo copies, microfilm etc.

e) Written records required by this part shall be maintained so that the data can be evaluated at least annually, for determining the quality standards of the drug product, need for changed in drug product specifications or manufacturing or control procedures. Written procedures shall be established and followed for such evaluations and shall include provisions for:

1) A review of representative number of batches, whether approved or rejected and where applicable records associated with the batches.

2) A review of the complaints, recalls, returned or salvaged drug products and investigations conducted under 211.192 for each drug product.


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Training Division


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, 211.204 or 211.208 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.

211.182 Equipment Cleaning and use log:

A written record of major equipment cleaning, maintenance and use shall be included in individual equipment logs that show date, time, product and a lot number of each batch processed. If the equipment is dedicated to the manufacture of one product, then individual equipment logs are mot required, provided that lots or batches of such product follow in numerical order and are manufactured in numerical sequence in case where dedicated equipment is used, the records of cleaning,maintenance and use shall be part of the batch record.


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Training Division

211.184 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 if known; the receiving cods as specified in 211.80; and the date of receipt. The name and location of the prime manufacturer, if different from the supplier, shall be listed if known.

b) The results of any test examination performed(including those performed as required by 211.82(a), 211.84(d) or 211.122(a) and the conclusions derived there from.

c) An individual inventory record of each component, drug product container and closure and for each component, a reconciliation of the use of each lot of such component. The inventory shall contain sufficient detail to allow determination of any batch or lot of drug product associated with the use of each component, drug product container and closure.


82QA APL U – XII

Training Division

211.184 Component, drug product container, closure and labeling records:

d) Documentation of the examination and review of labels and labeling for conformity with established specifications in accord with 211.122(c) and 211.130 (c ) .

e) The disposition of rejected components, drug product containers, closure and labeling.

211.186 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 thereof, shall be prepared dated, and signed 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 procedures shall be followed.

b) Master production and control records shall include:

1) The name and strength of the product and a description of the dosage form.


83QA APL U – XII

Training Division


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 or per unit weight or measure of the drug product, and a statement of the total weight or measure of any dosage unit.

3) A complete list of components designated by names or codes sufficiently specific to indicate any special quality characteristics.

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 they should be justified.

5) Statement concerning any calculated excess of component.


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Training Division


6) A statement of theoretical weight or measure at appropriate phases of processing;

7) A statement of theoretical yield, including the maximum and minimum percentages of theoretical yield beyond which investigation according to 211.192 is required;

8) A description of the drug product containers, closures and packaging materials, including specimen 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 are to be followed.


85QA APL U – XII

Training Division

211.188 Batch production and control records:

Each batch of drug product shall have a batch production record. it shall contain complete information relating to the production and control of the batch. These records shall include.

a) An accurate reproduction of the appropriate master production record or control record, checked for accuracy, dated and signed.

b) Documentation that each significant step in the manufacture, processing, packaging or holding of the batch was accomplished, including;

1) Dates;

2) Identity of individual major equipment and lines used;

3) Specific instrumentation of each batch of component or in-process material used.

4) Weights and measures of components used in the course of processing

5) Inprocess and laboratory control results

6) Labeling and packing areas inspection


86QA APL U – XII

Training Division

211.188 Batch production and control records:

7) A statement of the actual yield and a statement of the percentage of theoretical yield at appropriate phase of processing.

8) Complete labeling control records, including specimens or copies of all labels used

9) Description of the drug product containers and closures used.

10) Any sampling performed

11) Identification of the persons performing and directly supervising or checking significant steps in the operation.

12) Any investigation made according to 211.192

13) Results of the examinations made in accordance with 211.134


87QA APL U – XII

Training Division

211.192 Production Record Review:

All drug product production and control records, including those for packing 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. As unexplained discrepancy or the failure of a batch or any of its components to meet any of its specifications shall be thoroughly investigated whether or not the batch has already been distributed.

211.194 Laboratory Records:

a) Laboratory records shall include complete data derived from all tests to assure compliance with established specifications and standards, including examinations and assays. As follows.

1) Description of the sample received for testing with identification of source, quantity, lot number or other distinctive code, date on which sample is taken etc.

2) A statement of each method used in the testing of the sample. The suitability of all testing methods used shall be verified under actual conditions of use.


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Training Division


3) Statement of the weight or measure of sample used for each test, where appropriate.

4) Complete record of all data secured in course of each test, including graphs, charts and spectra, properly identified to show the specific component, drug product container, closure, inprocess material etc.

5) Record of all calculations of test, including units of measure, conversion factors equivalence factors etc.

6) A statement of results, how results are compared with established standards of identity, strength, quality and purity fot the component.

7) The initials of the person who performed the test and date.

8) Initials and date of the second person showing that the original record have been reviewed for accuracy, completeness and compliance.


89QA APL U – XII

Training Division


a) Complete records shall be maintained of any modifications of any modification of an established method employed in testing. Such records shall include reason for modification.reviewed for accuracy, completeness and compliance.

b) Records of any testing and standardization shall be maintained. Of laboratory reference standards, reagents and standard solutions.

c) Records for periodic calibration of laboratory instruments, apparatus, gauges and recording devices required by 211.160(b)(4)

d) Complete records shall be maintained of all stability testing performed in accordance with 211.166

211.196 Distribution Records:

Distribution records shall contain name, strength of product and description of dosage form, name and address of the consignee, date and quantity shipped, lot number etc.


90QA APL U – XII

Training Division

211.198 Complaints files:

a) Written procedures describing handling of all written and oral complaints regarding the drug product shall be established and followed. Such provisions shall include provisions for review by the quality control unit. If the drug product fails to meets the specifications an investigation shall be carried on as pre procedures.

b) A written record for each compliant shall be maintained in a file designated for drug product complaints.the complaints record file shall be filed up along with other manufacturing, packing records and shall be easily retrievable. They shall be retained Atleast 1 year after expiration date.

1) Written records shall include following information, wherte known the name and strength of the drug product, lot number, name of the complaint, nature of the compliant and reply to compliant.

2) Where an investigation is conducted the finding of the same and follow-ups shall be recorded.

3) Where an investigation was not conducted, a written record shall include the reason that an investigation was found not to be necessary and the name of the responsible person


91QA APL U – XII

Training Division

211.204 Returned drug products:

Returned drug products shall be identified as such and held. If the different conditions under which the returned products, casts doubt on the safety, identity, strength, quality or purity of the drug product, the returned goods shall be destroyed, unless the examination shall prove that the product meets the quality requirements. The drug may be reprocessed if it is found to meet appropriate standards, specifications and characteristics. Records of such returned drug products shall be maintained.

211.208 Drug product salvaging

drug products subjected to improper storage conditions including extremes in temperature, humidity, smoke, fumes, pressure or radiations shall not be salvaged and returned to market place. Salvaging operations may be conducted only if there is

Evidence from laboratory tests and assays that the drug products meet all the applicable standards of identity, strength, quality and purity.

Evidence from the inspection of the premises that the drug products and their associated packing materials were not subjected to improper storage conditions.

What does ORANGE GUIDE tells about Quality Aspects

PART 211Sub Part K – Returned and Salvaged Drug Products

92QA APL U – XII

Training Division

QUALITY MANAGEMENT

QUALITY MANAGEMENT

DOCUMENTATION

QUALITY CONTROL

Documentation

Sampling

Testing

CONTRACT MANUFACTURER AND ANALYSIS

Contract Giver

Contract Acceptor

93QA APL U – XII

Training Division

QUALITY MANAGEMENT

COMPLAINTS AND PRODUCT RECALLS

Complaints

Recalls

SELF INSPECTION

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Training Division

QUALITY MANAGEMENT

QUALITY MANAGEMENT.

The holder of a manufacturing authorization must manufacture medicinal products so as to ensure that.

They are fit for their intended use

Comply with the requirements of the marketing authorization

Products are safe and therapeutically effective

Attainment of quality objective is the responsibility of “SENIOR MANAGEMENT” and requires participation and commitment of people at all levels within and outside.

95QA APL U – XII

Training Division

QUALITY MANAGEMENT

TO ACHIEVE QUALITY OBJECTIVE

There must be a comprehensively

designed and correctively implemented

system of QA, which should be fully

documented and its effectiveness

monitored.

96QA APL U – XII

Training Division

DOCUMENTATION

Documentation should be approved, signed and dated by authorized persons.

Documents should have unambiguous contents. Purpose should be clearly stated.

Reproduced documents should be clear and legible.

Documents should be regularly reviewed and kept up to date.

There must be a system to retrieve superseded documents before issuing revised one. (controlled concept).

Documents should not be hand written, however data recording by hand is acceptable if clear and legible

97QA APL U – XII

Training Division

DOCUMENTATION

Any alteration, should be signed and dated with reason for alteration. The alteration should permit the reading of original information.

Records should be retrained for at least one year after the expiry of product.

The records should be made or completed at the time, each action is taken.

Batch records, electrically stored should be protected by backup support.

There should be approved and dated specifications for RM / PM / In process / Bulk / Finished products.

98QA APL U – XII

Training Division

DOCUMENTATION

Authorized manufacturing formula and processing instructions should exists for each product and batch size.

There should be authorized packaging instructions for each product, pack size and type.

Batch processing record and batch packing records should be kept for each batch processed / packed.

Line clearance records, wherever required should be recorded.

There should be written and approved procedure of each and every activity being carried out in the plant (SOP’s).

99QA APL U – XII

Training Division

DOCUMENTATION

There should be written procedures and the associated records for.

Validation

Calibration

Equipment assembly (IQ, OQ)

Maintenance, cleaning and sanitization

Training

Environmental monitoring

Complaints, Recalls, Returns

Pest and Rodent Controls

Machine usage log books should be maintained.

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Training Division

QUALITY CONTROL

QC department should be independent for mother departments and under the authority of a person with appropriate qualifications and experience.

Should have adequate, experienced and qualified staff to carry out various activities.

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Training Division

QUALITY CONTROL

Documentation

Following shall be readily available with QC.

Specifications

Sampling procedures

Test procedures

Record including analytical work sheets and / or laboratory note books.

Analytical reports

Environmental monitoring data

Validation records of test methods

Calibration records of instruments

Equipment maintenance records

102QA APL U – XII

Training Division

QUALITY CONTROL

Documentation

Trend data for analytical test results, yields, environmental control etc. should be available .

Original data such as laboratory note books should be retained and readily available.

103QA APL U – XII

Training Division

QUALITY CONTROL

Sampling

Sampling procedure should include, method of sampling, equipment to be used, sampling quantity and instructions for any subdivision of the sample, type of sample container, special precautions for sterile materials, storage conditions etc.

Reference samples should be batch representative.

Sample containers should bear label, indicating materials name, sample data and container number.

Reference samples of finished goods should be retained up to one year after the expiry data, in their final pack.

104QA APL U – XII

Training Division

QUALITY CONTROL

Sampling

Samples of raw materials should be retained for at least two years after the release of the product.

Reference samples should be of a size sufficient to permit at least a full reexamination.

Analytical methods should be validated.

Testing

Testing should be carried out accordingly to approved methods only.

Calculations should be critically examined.

Test performed should be recorded.

105QA APL U – XII

Training Division

QUALITY CONTROL

Testing

Laboratory reagents, volumetric solutions, reference standards and culture media should be prepared in accordance with written procedures.

Standard solutions should be marked with preparation data, signature of person who prepared it, use before, storage condition, next standardization date and last current factor.

Date of receipt of any substances used for testing operations should be indicated on the container.

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Training Division

CONTRACT MANUFACTURE AND ANALYSIS

There must be a written contract between contract giver and contract acceptor, which clearly establishes the duties of each party.

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Training Division


Contract Given

Contract giver is responsible for assessing the competence of the contract acceptor.

Contract giver should provide the contract acceptor with all the information necessary to carry out the contracted operations, correctly.

Contract given should ensure that products delivered to him by contract acceptor comply with specifications and released by their QP.

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Training Division


Contract Given

Contract acceptor should not pass to a third party any of the work entrusted to him under contract.

Contract should specify the responsibilities of both contract giver and acceptor.

The contract should permit the contract giver to visit the facilities of the contract acceptor.

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Training Division


Complaints

A person should be designed as responsible for handling complaints.

QP should be made aware of complaint.

There should be a written procedure for handling complaints or for recalls

Complaints should be thoroughly investigated, involving QC as well.

If a product defect is discovered, other batches which may contain reworks of defective batch should also be investigated.

All decisions and measures taken as a result of compliant should be recorded and referenced to the corresponding batch records.

110QA APL U – XII

Training Division


Complaints

Complaint records should be reviewed regularly for any indication of specific or recurring problems, requiring attention.

Recalls

A person should be designed as responsible for execution and coordination for recalls and should be supported by sufficient staff to handle all aspects of recall with degree of urgency.

There should be a written recall procedure.

Distribution records should be readily available to the person responsible for recalls

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Training Division


Recalls

Address, telephone or fax numbers of all distributors, whole sellers and directly supplied customers should be available.

Recalled products should be stored separately in a secure way.

Progress of recall process should be recorded.

Reconciliation of delivered quantity and recovered quantity should be done.

Effectiveness of recall producer should be evaluated from time to time.

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Training Division

SELF INSPECTION

SELF INSPECTION

Self inspection should be conducted in order to monitor the implementation and compliance with GMP’s.

Self inspection should be conducted in an independent way by designated competent persons from within / outside.

Self inspections should be recorded.

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Training Division

SAMPLING OF STARTING MATERIALS AND PACKING MATERIALS

Raw Materials

Individual samples taken form all containers and identification test on each sample. It is permissible to sample only few containers, where a validated procedure has been established to ensure that no container has been incorrectly labeled (Vendor Confidence and History)

Packing Materials

Company’s own statistical sampling plan

End Session