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GOOD MANUFACTURING PRACTICES FOR PHARMACEUTICALS

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GOOD MANUFACTURING PRACTICES FOR PHARMACEUTICALS By Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D Department of Pharmaceutics Omar Al-Mukthar University – PowerPoint PPT presentation

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Title: GOOD MANUFACTURING PRACTICES FOR PHARMACEUTICALS


1
GOOD MANUFACTURING PRACTICES FOR PHARMACEUTICALS
  • By
  • Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D
  • Department of Pharmaceutics
  • Omar Al-Mukthar University
  • Al-Bayda, Libya.
  • E-mail nanjwadebk_at_gmail.com

2
CONTENTS
  • Current GMP in manufacturing processes
  • Packaging and holding of drugs
  • Finished pharmaceuticals
  • General provisions
  • Organization and personnel
  • Building and facilities
  • Equipment
  • Control of components
  • Containers and closures
  • Production and process control
  • Packaging and labeling control
  • Holding and distribution
  • Records and reports
  • Returned savaged drug products
  • The inspection for compliance with GMP
    regulations
  • Controlled substances safeguards
  • References

3
Introduction
4
What is GMP ?
  • GMP is that part of Quality assurance which
    ensures that the products are consistently
    manufactured and controlled to the Quality
    standards appropriate to their intended use
  • A set of principles and procedures which, when
    followed by manufacturers for therapeutic goods,
    helps ensure that the products manufacture will
    have the required quality.

5
Good Manufacturing Practices
  • A basic tenet of GMP is that quality cannot be
    tested into a batch of product but must be built
    into each batch of product during all stages of
    the manufacturing process.
  • It is designed to minimize the risks involved in
    any pharmaceutical production that cannot be
    eliminated through testing the final product.

6
Some of the main risks are
  • unexpected contamination of products, causing
    damage to health or even death.
  • incorrect labels on containers, which could mean
    that patients receive the wrong medicine.
  • insufficient or too much active ingredient,
    resulting in ineffective treatment or adverse
    effects.

7
Why GMP is important
  • A poor quality medicine may contain toxic
    substances that have been unintentionally added.
  • A medicine that contains little or none of the
    claimed ingredient will not have the intended
    therapeutic effect.

8
GMP
QA
GMP
QC
9
QA, GMP QC inter-relationship
  • It is the sum total of the organized
    arrangements with the objective of ensuring that
    products will be of the quality required for
    their intended use

QA
10
GMP
GMP
Is that part of Quality Assurance aimed at
ensuring that products are consistently
manufactured to a quality appropriate to their
intended use
11
QA, GMP QC inter-relationship
  • Is that part of GMP concerned with sampling,
    specification testing, documentation release
    procedures which ensure that the necessary
    relevant tests are performed the product is
    released for use only after ascertaining its
    quality

QC
12
QC and QA
  • QC is that part of GMP which is concerned with
    sampling,
  • specifications, testing and with in the
    organization, documentation,and release
    procedures which ensure that the necessary and
    relevant tests are carried out
  • QA is the sum total of organized arrangements
    made with the object of ensuring that product
    will be of the Quality required by their intended
    use.

13
QC and QA
  • Operational laboratory techniques and activities
    used to fulfill the requirement of Quality
  • All those planned or systematic actions necessary
    to provide adequate confidence that a product
    will satisfy the requirements for quality

14
QC and QA
  • QC is lab based
  • QA is company based

15
GMP
  • The Quality of a formulation or a bulk drug
    depends on the Quality of those producing it
  • GMP is the magic key that opens the door of the
    Quality
  • In matter of GMP, swim with the current and
  • in matter of Quality stand like a rock!

16
GMP helps boost pharmaceutical export
opportunities
  • Most countries will only accept import and sale
    of medicines that have been manufactured to
    internationally recognized GMP.
  • Governments seeking to promote their countries
    export of pharmaceuticals can do so by making GMP
    mandatory for all pharmaceutical production and
    by training their inspectors in GMP requirements.

17
GMP Covers
  • ALL aspects of production from the starting
    materials, premises and equipment to the training
    and personal hygiene of staff.
  • Detailed, written procedures are essential for
    each process that could affect the quality of the
    finished product.
  • There must be systems to provide documented proof
    that correct procedures are consistently followed
    at each step in the manufacturing process - every
    time a product is made.

18
GMP guidelines
  • GMP as per Schedule M
  • GMP as per WHO
  • GMP as per MCA now known as MHRA
  • GMP as per TGA
  • GMP as per US FDA
  • GMP as per ICH guidelines

19
GMP guidelines
  • GMP as per Schedule M
  • www.cdsco.nic.in
  • GMP as per WHO
  • www.who.int
  • GMP as per MCA now known as MHRA
  • www.mca.gov.uk
  • GMP as per TGA
  • www.tga.gov.au
  • GMP as per US FDA
  • www.fda.gov
  • GMP as per ICH guidelines
  • www.ich.org

20
GMP guidance documents
  • EU Good Manufacturing Practice (GMP) Guidelines,
    Volume 4 of The rules governing medicinal
    products in the European Union
  • US FDA current Good Manufacturing Practice (cGMP)
    for finished pharmaceuticals, 21 CFR, 210 and 211
  • WHO Good Manufacturing Practices for
    pharmaceutical products, Annex 4 to WHO Technical
    Report Series, No. 908, 2003

21
GMP
  • GMP in solid dosage forms
  • GMP in semisolid dosage forms
  • GMP in Liquid orals
  • GMP in Parenterals Production
  • GMP in Ayurvedic medicines
  • GMP in Bio technological products
  • GMP in Nutraceuticals and cosmeceuticals

22
Ten Principles of GMP
  • Design and construct the facilities and
    equipments properly
  • Follow written procedures and Instructions
  • Document work
  • Validate work
  • Monitor facilities and equipment
  • Write step by step operating procedures and work
    on instructions
  • Design ,develop and demonstrate job competence
  • Protect against contamination
  • Control components and product related processes
  • Conduct planned and periodic audits

23
List of important documents in GMP
  • Policies
  • SOP
  • Specifications
  • MFR (Master Formula Record)
  • BMR
  • Manuals
  • Master plans/ files
  • Validation protocols
  • Forms and Formats
  • Records

24
10 attributes of a good document
  • Accurate
  • Clear
  • Complete
  • Consistent
  • Indelible
  • Legible
  • Timely
  • Direct
  • Authentic
  • Authorized

25
Beyond GMP
  • Reduce pollution -? Zero discharge
  • Adaptation of environment friendly methods
  • Consideration for better and healthier life
    tomorrow
  • Consideration of ethics in life
  • One should begin with end in mind otherwise it
    will be the beginning of the end

26
API Manufacturing Process
27
Secondary Manufacturing Dosage Forms
28
Secondary Manufacturing Process - Tablets
29
Secondary Manufacturing Process Sterile
parenteral for injection
30
Biotechnology Manufacturing Process
31
Current GMP in manufacturing processes (cGMP)
32
What are cGMPs?
  • cGMP refers to the Current Good Manufacturing
    Practice regulations enforced by the US Food and
    Drug Administration (FDA).
  • cGMP provide for systems that assure proper
    design, monitoring and control of manufacturing
    processes and facilities.
  • Adherence to the cGMP regulations assures the
    identity, strength, quality and purity of drug
    products by requiring that manufacturers of
    medications adequately control manufacturing
    operations

33
What are cGMPs?
  • This includes establishing strong quality
    management systems, obtaining appropriate quality
    raw materials, establishing robust operating
    procedures, detecting and investigating product
    quality deviations, and maintaining reliable
    testing laboratories.
  • This formal system of controls at a
    pharmaceutical company, if adequately put into
    practice, helps to prevent instances of
    contamination, mix-ups, deviations, failures, and
    errors.
  • This assures that drug products meet their
    quality standards.

34
What are cGMPs?
  • The cGMP requirements were established to be
    flexible in order to allow each manufacturer to
    decide individually how to best implement the
    necessary controls by using scientifically sound
    design, processing methods, and testing
    procedures.
  • The flexibility in these regulations allows
    companies to use modern technologies and
    innovative approaches to achieve higher quality
    through continual improvement.

35
What are cGMPs?
  • Accordingly the c in cGMP stands for current
    requiring companies to use technologies and
    systems that are up-to-date in order to company
    with the regulations.
  • Systems and equipment that may have been
    top-of-the-line to prevent contamination,
    mix-ups, and errors 10 or 20 years ago may be
    less than adequate by todays standards.

36
What are cGMPs?
  • It is important to note that cGMP are minimum
    requirements.
  • Many pharmaceutical manufacturers are already
    implementing comprehensive, modern quality
    systems and risk management approaches that
    exceed these minimum standards.

37
Why are cGMP so important
  • A consumer usually cannot detect (through smell,
    touch, or sight) that a drug product is safe or
    if it will work.
  • While cGMPs require testing, testing alone is not
    adequate to ensure quality.
  • In most instances testing is done on a small
    sample of a batch (for example, a drug
    manufacturer may test 1000 tablets from a batch
    that contains 2 million tablets), so that most of
    the batch can be used for patients rather than
    destroyed by testing.

38
Why are cGMP so important
  • Therefore, it is important that drugs are
    manufactured under conditions and practices
    required by the cGMP regulations to assure that
    quality is built into the design and
    manufacturing process at every step.
  • Facilities that are in good conditions, equipment
    that is properly maintained and calibrated,
    employees who are qualified and fully trained,
    and processes that are reliable and reproducible,
    are a few examples of how cGMP requirements help
    to assure the safety and efficacy of drug
    products.

39
Packaging
40
Packaging
41
Packaging
42
Packaging and holding of drugs
  • Care shall be taken when using automatic tablet
    and capsule counting, strip and blister packaging
    equipment to ensure that all rogue tablets,
    capsules or foils from packaging operation are
    removed before a new packaging operation is
    commenced.
  • There shall be an independent recorded check of
    the equipment before a new batch of tablets or
    capsules is handled.

43
Packaging and holding of drugs
  • Uncoated tablets shall be packed on equipment
    designed to minimize the risk of
    cross-contamination. Such packaging shall be
    carried out in an isolated area when potent
    tablets or Beta-Iactum containing tablets are
    being packed.
  • The strips coming out of the machine shall be
    inspected for defects such as misprint, cuts on
    the foil, missing tablets and improper sealing.

44
Packaging and holding of drugs
  • Integrity of individual packaging strips and
    blisters shall be subjected to vacuum test
    periodically to ensure leak proofness of each
    pocket strip and blister and records maintained.

45
Finished pharmaceuticals
  • Appropriate specifications for finished products
    shall include -
  • The designated name of the product and the code
    reference.
  • The formula or a reference to the formula and the
    pharmacopoeial reference.
  • Directions for sampling and testing or a
    reference to procedures.

46
Finished pharmaceuticals
  • A description of the dosage form and package
    details.
  • The qualitative and quantitative requirements,
    with the acceptance limits for release.
  • The storage conditions and precautions, where
    applicable, and the shelf-life.

47
General provisions
  • The processing of dry materials and products
    creates problems of dust control and
    cross-contamination. Special attention is
    therefore, needed in the design, maintenance and
    use of premises and equipment in order to
    overcome these problems. Wherever required,
    enclosed dust control manufacturing systems shall
    be employed.

48
General provisions
  • Suitable environmental conditions for the
    products handled shall be maintained by
    installation of air-conditioning wherever
    necessary. Effective air extraction systems, with
    discharge points situated to avoid contamination
    of other products and professes shall be
    provided. Filters shall be installed to retain
    dust and protect the factory and local environment

49
General provisions
  • Special care shall be taken to protect against
    subsequent contamination of the product by
    particles of metal or wood. The use of metal
    detector is recommended. Wooden equipment should
    be avoided. Screens, sieves, punches and dies
    shall be examined for wear and tear or for
    breakage before and after each use.

50
General provisions
  • All ingredients for a dry product shall be sifted
    before use unless the quality of the input
    material can be assured. Such sifting shall
    normally be carried out at dedicated areas.
  • Where the facilities are designed to provide
    special environmental conditions of pressure
    differentials between rooms, these conditions
    shall be regularly monitored and any
    specification results brought to the immediate
    attention of the Production and quality Assurance
    Department which shall be immediately attended to.

51
General provisions
  • Care shall be taken to guard against any material
    lodging and remaining undetected in any
    processing or packaging equipment. Particular
    care shall be taken to ensure that any vacuum,
    compressed air or air-extraction nozzles are kept
    clean and that there is no evidence lubricants
    leaking into the product from any part of the
    equipment.

52
Organization and personnel
  • Responsibilities of quality control unit.
  • Personnel qualifications.
  • Personnel responsibilities.
  • Consultants.

53
Organization and personnel
  • The manufacture shall be conducted under the
    direct supervision of competent technical staff
    with prescribed qualifications and practical
    experience in the relevant dosage and/or active
    pharmaceutical products.
  • The head of the Quality Control Laboratory shall
    be independent of the manufacturing unit. The
    testing shall be conducted under the direct
    supervision of competent technical staff who
    shall be whole time employees of the licensee.

54
Organization and personnel
  • Personnel for Quality Assurance and Quality
    Control operations shall be suitably qualified
    and experienced.
  • Written duties of technical and Quality Control
    personnel shall be laid and following strictly.
  • Number of personnel employed shall be adequate
    and in direct proportion to the workload.
  • The licensee shall ensure in accordance with a
    written instruction that all personnel in
    production area or into Quality Control
    Laboratories shall receive training appropriate
    to the duties and responsibility assigned to
    them. They shall be provided with regular
    in-service training.

55
Building and facilities
  1. Design and construction features.
  2. Lighting.
  3. Ventilation, air filtration, air heating and
    cooling.
  4. Plumbing.
  5. Sewage and refuse.
  6. Washing and toilet facilities.
  7. Sanitation.
  8. Maintenance.

56
Building and facilities
  • The building(s) used for the factory shall be
    designed, constructed, adapted and maintained to
    suit the manufacturing operations so as to permit
    production of drugs under hygienic conditions.
    They shall conform to the conditions laid down in
    the Factories Act.

57
Building and facilities
  • The premises used for manufacturing, processing,
    warehousing, packaging labeling and testing
    purposes.
  • Compatible with other drug manufacturing
    operations that may be carried out in the same or
    adjacent area / section.

58
Building and facilities
  • Adequately provided with working space to allow
    orderly and logical placement of equipment,
    materials and movement of personnel so as to
  • avoid the risk of mix-up between different
    categories of drugs or with raw materials,
    intermediates and in-process material.
  • avoid the possibilities of contamination and
    cross- contamination by providing suitable
    mechanism.

59
Building and facilities
  • Designed/constructed/maintained to prevent entry
    of insects, pests, birds, vermins, and rodents.
    Interior surface (walls, floors and ceilings)
    shall be smooth and free from cracks, and permit
    easy cleaning, painting and disinfection.

60
Building and facilities
  • Air-conditioned, where prescribed for the
    operations and dosage froms under production. The
    production and dispensing areas shall be well
    lighted, effectively ventilated, with air control
    facilities and may have proper Air Handling Units
    (wherever applicable) to maintain conditions
    including temperature and, wherever necessary,
    humidity, as defined for the relevant product.
    These conditions shall be appropriate to the
    category of drugs and nature of the operation.
    These shall also be suitable to the comforts of
    the personnel working with protective clothing,
    products handled, operations undertaken within
    them in relation to the external environment.
    These areas shall be regularly monitored for
    compliance with required specifications

61
Building and facilities
  • Provided with drainage system, as specified for
    the various categories of products, which shall
    be of adequate size and so designed as to prevent
    back flow and/or prevent insects and rodents
    entering the premises. Open channels shall be
    avoided in manufacturing areas and, where
    provided, these shall be shallow to facilitate
    cleaning and disinfection

62
Building and facilities
  • The walls and floors of the areas where
    manufacture of drugs is carried out shall be free
    from cracks and open joints to avoid accumulation
    of dust. These shall be smooth, washable, covered
    and shall permit easy and effective cleaning and
    dis-infection. The interior surfaces shall not
    shed particles. A periodical record of cleaning
    and painting of the premises shall be maintained.

63
Equipment
  • Equipment design, size, and location.
  • Equipment construction.
  • Equipment cleaning and maintenance.
  • Automatic, mechanical, and electronic equipment.
  • Filters.

64
Equipment
  • Equipment shall be located, designed,
    constructed, adapted and maintained to suit the
    operations to be carried out. The layout and
    design of the equipment shall aim to minimise the
    risk of errors and permit effective cleaning and
    maintenance in order to avoid cross-contamination,
    build-up of dust or dirt and, in general any
    adverse effect on the quality of products. Each
    equipment shall be provided with a logbook,
    wherever necessary.

65
Equipment
  • Balances and other measuring equipment of an
    appropriate range, accuracy and precision shall
    be available in the raw material stores,
    production and in process control operations and
    these shall be calibrated and checked on a
    scheduled basis in accordance with Standard
    Operating Procedures and records maintained.

66
Equipment
  • The parts of the production equipment that come
    into contact with the product shall not be
    reactive, additive or adsorptive to an extent
    that would affect the quality of the product.
  • To avoid accidental contamination, wherever
    possible, non-toxic/edible grade lubricants shall
    be used and the equipment shall be maintained in
    a way that lubricants do not contaminate the
    products being produced.

67
Equipment
  • Defective equipment shall be removed from
    production and Quality Control areas or
    appropriately labeled.

68
Control of components
  • General requirements.
  • Receipt storage of untested components, drug
    product containers, and closures.
  • Testing and approval or rejection of components,
    drug product containers, and closures.
  • Use of approved components, drug product
    containers, and closures.
  • Retesting of approved components, drug product
    containers, and closures.
  • Rejected components, drug product containers, and
    closures.
  • Drug product containers and closures.

69
Control of components
  • Each tablets compressing machine shall be
    provided with effective dust control facilities
    to avoid cross-contamination. Unless the same
    product is being made on each machine, or unless
    the compression machine itself provides its own
    enclosed air controlled environment, the machine
    shall be installed in separate cubicles.

70
Control of components
  • Suitable physical procedural and labeling
    arrangements shall be made to prevent mix up of
    materials, granules and tables on compression
    machinery.
  • Accurate and calibrated weighting equipment shall
    be readily available and used for in-process
    monitoring of tablet weight variation. Procedures
    used shall be capable of detecting out-of-limits
    tablets.

71
Control of components
  • At the commencement of each compression run and
    in case of multiple compression points in a
    compression machine, sufficient individual
    tablets shall be examined at fixed intervals to
    ensure that a tablet from each compression
    station or from each compression point has been
    inspected for suitable pharmacopoeial parameters
    like appearance, weight variation,
    disintegration, hardness, friability and
    thickness. The results shall be recorded as
    part of the batch documentation.

72
Control of components
  • Tablets shall be de-dusted, preferably by
    automatic device and shall be monitored for the
    presence of foreign materials besides any other
    defects.
  • Tablets shall be collected into clean, labeled
    containers.
  • Rejected or discarded tablets shall be isolated
    in identified containers and their quality
    recorded in the Batch Manufacturing Record.

73
Control of components
  • In-process control shall be employed to ensure
    that the products remain within specification.
    During compression, samples of tablets shall be
    taken at regular intervals of not greater than 30
    minutes to ensure that they are being produced in
    compliance with specified in-process
    specification. The tablets shall also be
    periodically checked for additional parameters
    such as appearance, weight variation,
    disintegration, hardness, friability and
    thickness and contamination by lubricating oil.

74
Containers and closures
  • All containers and closures intended for use
    shall comply with the pharmacopoeial
    requirements. Suitable validated test methods,
    sample sizes, specifications, cleaning procedure
    and sterilization procedure, wherever indicated,
    shall be strictly followed to ensure that these
    are not reactive, additive, absorptive, or leach
    to an extent that significantly affects the
    quality or purity of the drug. No second hand or
    used containers and closures shall be used.

75
Containers and closures
  • Whenever bottles are being used, the written
    schedule of cleaning shall be laid down and
    followed. Where bottles are not dried after
    washing, they should be rinsed with de-ionised
    water or distilled water, as the case may be.
  • For in-process and bulk products. -
    Specifications for in-process material,
    intermediate and bulk products shall be
    available. The specifications should be
    authenticated.

76
Containers and closures
  • All containers and closures intended for use
    shall comply with the pharmacopoeial and other
    specified requirements. Suitable samples sizes,
    specifications, test methods, cleaning procedures
    and sterilization procedures, shall be used to
    assure that containers, closures and other
    component parts of drug packages are suitable and
    are not reactive, additive, adsorptive or
    leachable or presents the risk of toxicity to an
    extent that significantly affects the quality or
    purity of the drug. No second hand or used
    containers and closures shall be used.

77
Containers and closures
  • Plastic granules shall also comply with the
    pharmacopoeial requirements including
    physio-chemical and biological tests.
  • All containers and closures shall be rinsed prior
    to sterilization with Water for Injection
    according to written procedure.
  • The design of closures, containers and stoppers
    shall be such as to make cleaning, easy and also
    to make airtight seal when fitted to the bottles.

78
Containers and closures
  • It shall be ensured that containers and closures
    chosen for a particular product are such that
    when coming into contact they are not absorbed
    into the product and they do not affect the
    product adversely. The closures and stoppers
    should be of such quality substances as not to
    affect the quality of the product and avoid the
    risk of toxicity.

79
Containers and closures
  • Whenever glass bottles are used, the written
    schedule of cleaning shall be laid down and
    followed. Where bottles are not dried after
    washing, these shall be finally rinsed with
    distilled water or pyrogen free water, as the
    case may be, according to written procedure.
  • Individual containers of parenteral preparations,
    ophthalmic preparations shall be examined against
    black/white background fitted with diffused light
    after filling so as to ensure freedom from
    foreign matters.

80
Containers and closures
  • Glass Bottles-
  • Shape and design of the glass bottle shall be
    rational and standardized. Glass bottles made of
    USP Type-I and USP Type-II glass shall only be
    used. Glass bottles shall not be reused. Before
    use, USP Type-II bottles shall be validated for
    the absence of particulate matter generated over
    a period of the shelf life of the product and
    shall be regularly monitored after the
    production, following statistical sampling
    methods. USP Type-III glass containers may be
    used for non-parenteral sterile products such as
    Otic Solutions.

81
Containers and closures
  • Plastic Containers.-
  • Pre-formed plastic containers intended to be used
    for packing of Large Volume Parenteral shall be
    moulded in-house by one-continuous operation
    through an automatic machine.
  • Blowing, filling and sealing (plugging) operation
    shall be conducted in room(s) conforming to
    requirements as mentioned in Table III of Item
    3.10. Entry to the area where such operations are
    undertaken, shall be through a series of
    airlocks. Blowers shall have an air supply which
    is filtered through 0.22µ filters. Removal of
    runners and plugging operations shall be
    conducted under a laminar airflow workstation.

82
Containers and closures
  • Rubber Stoppers-
  • The tuber stoppers used for Large Volume
    Parenterals shall comply with specifications
    prescribed in the current edition of the Indian
    Pharmacopoeia.

83
Production and process control
  • Written procedures deviations.
  • Charge-in of components.
  • Calculation of yield.
  • Equipment identification.
  • Sampling and testing of in-process materials and
    drug products.
  • Time limitations on production.
  • Control of microbiological contamination.
  • Reprocessing.

84
Production and process control
  • Production control is a process of making sure
    that production is constantly maintained to
    produce the products of given specifications.
  • Control process have several aspects, such as raw
    materials, tools, in-process materials and
    finished products.

85
Production and process control
  • Production control process can be made effective
    by
  • Setting standards
  • Measuring the job performing
  • Getting feedback of results
  • Taking corrective action
  • Production controls are to ensure that orders are
    not misunderstood, standards are not violated and
    objectives are not shifted unknowing. It is a
    means of building quality.

86
Packaging and labeling control
  • Materials examination and usage criteria.
  • Labeling issuance.
  • Packaging and labeling operations.
  • Tamper-evident packaging requirements for
    over-the-counter (OTC) human drug products.
  • Drug product inspection.
  • Expiration dating.

87
Packaging and labeling control
  • Care shall be taken when using automatic tablet
    and capsule counting, strip and blister packaging
    equipment to ensure that all rogue tablets,
    capsules or foils from packaging operation are
    removed before a new packaging operation is
    commenced. There shall be an independent recorded
    check of the equipment before a new batch of
    tablets or capsules is handled.

88
Packaging and labeling control
  • Uncoated tablets shall be packed on equipment
    designed to minimize the risk of
    cross-contamination. Such packaging shall be
    carried out in an isolated area when potent
    tablets or Beta-Iactum containing tablets are
    being packed.
  • The strips coming out of the machine shall be
    inspected for defects such as misprint, cuts on
    the foil, missing tablets and improper sealing.

89
Packaging and labeling control
  • Integrity of individual packaging strips and
    blisters shall be subjected to vacuum test
    periodically to ensure leak proofness of each
    pocket strip and blister and records maintained.

90
Packaging and labeling control
91
Holding and distribution
  • Warehousing procedures.
  • Distribution procedures.

92
Holding and distribution
  • Prior to distribution or dispatch of given batch
    of a drug, it shall be ensure that the batch has
    been duly tested, approved and released by the
    quality control personnel. Pre-dispatch
    inspection shall be performed on each consignment
    on a random basis to ensure that only the correct
    goods are dispatched. Detailed instructions for
    warehousing and stocking of Large Volume
    Parenterals, if stocked, shall be in existence
    and shall be complied with after the batch is
    released for distribution. Periodic audits of
    warehousing practices followed at distribution
    centers shall be carried out and records thereof
    shall be maintained. Standard Operating
    Procedures shall be developed for warehousing of
    products.

93
Holding and distribution
94
Records and reports
  1. General requirements.
  2. Equipment cleaning and use log.
  3. Component, drug product container, closure, and
    labeling records.
  4. Master production and control records.
  5. Batch production and control records.
  6. Production record review.
  7. Laboratory records.
  8. Distribution records.
  9. Complaint files.

95
Records and reports
  • The licensee shall maintain records of different
    manufacturing activities with regard to each
    stage of manufacture in-process control,
    assembling, packing, batch records for the
    quantity of devices manufactured from each lot of
    blended granules, duration of work, hourly
    quantum of production in respect of each item as
    well as record of each sterilizing cycle of the
    gaseous method employed.

96
Records and reports
  • Records shall be maintained for all disposal of
    waste.
  • The records shall be made or completed at the
    time of each operation in such a way that all
    significant activities concerning the manufacture
    of pharmaceutical products are traceable.
  • Records and associated Standard Operating
    Procedures (SOP) shall be retained for at least
    one year after the expiry date of the finished
    product.

97
Records and reports
  • Records of receipt of all labeling and packaging
    materials shall be maintained for each shipment
    received indicating receipt, control reference
    numbers and whether accepted or rejected.

98
Records and reports
  • The records of the receipts shall include
  • a. The name of the material on the delivery note
    and the number of containers
  • b. The date of receipt
  • c. The manufacturers and/ or suppliers name
  • d. The manufacturers batch or reference number
  • e. The total quantity, and number of containers,
    quantity in each container received
  • f. The control reference number assigned after
    receipt
  • g. Any other relevant comment or information.

99
Records and reports
  • The manufacturing records
  • Serial number of the Batch Manufacturing Record.
  • Reference to Master Formula Record.
  • Filter integrity testing records
  • Leak test records.
  • Inspection records.
  • Container washing records.
  • Environmental monitoring records.

100
Records and reports
  • Reports of serious adverse drug reactions
    resulting from the use of a drug along with
    comments and documents shall be forthwith
    reported to the concerned licensing authority.
  • Reference numbers of relevant analytical reports.

101
Returned savaged drug products
  • Returned drug products.
  • Drug product salvaging.

102
Returned savaged drug products
  • Adequate areas shall be designed to allow
    sufficient and orderly warehousing of returned or
    recalled products.
  • Segregation shall be provided for the storage of
    rejected, recalled or returned materials or
    products.

103
The inspection for compliance with GMP
regulations
  • Short description of the self inspection system
    indicating whether an outside, independent and
    experienced external export was involved in
    evaluating the manufacturers compliance with
    Good manufacturing Practices in all aspects of
    production.
  • Periodic inspection of the garments shall be done
    by responsible staff.

104
The inspection for compliance with GMP
regulations
  • When inspection is done visually, it shall be
    done under suitably controlled conditions of
    illumination and background.
  • Operators doing the inspection shall pass regular
    eye-sight checks with spectacles, if worn, and be
    allowed frequent rest from inspection.
  • Where other methods of inspection are used, the
    process shall be validated and the performance of
    the equipment checked at suitable intervals.
    Results shall be recorded.

105
The inspection for compliance with GMP
regulations
  • Inspection of equipment for cleanliness
    immediately before use
  • Clarity testing inspection units.
  • Tablet Inspection unit/belt.
  • Visual inspection area
  • Medical inspection of workers at the time of
    employment and periodically check-up thereafter
    at least once a year.
  • Needle Inspection Unit.

106
Controlled substances safeguards
  • Hazardous, toxic substances and flammable
    materials shall be stored in suitably designed
    and segregated, enclosed areas in conformity with
    Central and State Legislations.
  • Highly hazardous, poisonous and explosive
    materials such as narcotics, psychotropic drugs
    and substances presenting potential risks of
    abuse, fire or explosion shall be stored in safe
    and secure areas. Adequate fire protection
    measures shall be provided in conformity with the
    rules of the concerned civic authority.

107
References
  • EU Good Manufacturing Practice (GMP) Guidelines,
    Volume 4 of The rules governing medicinal
    products in the European Union
  • US FDA current Good Manufacturing Practice (cGMP)
    for finished pharmaceuticals, 21 CFR, 210 and 211
  • WHO Good Manufacturing Practices for
    pharmaceutical products, Annex 4 to WHO Technical
    Report Series, No. 908, 2003

108
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