CURRENT GOOD

MANUFACTURING
PRACTICES
1. Objective
2. GENERAL REQUIREMENTS:
3. Warehousing Area:
4. Production area:
5. Ancillary Areas:
6. Quality Control Area.
7. Health, clothing and sanitation of workers:
8. Manufacturing Operations and Control:
9. Sanitation in the Manufacturing Premises:
10. Raw Materials:
11. Equipment:
12. Documentation and Records:–
13. Labels and other Printed Materials
14. Quality Assurance:–
15. Self Inspection and Quality audit:–
16. Quality Control System.

17. Specification

18. Master Formula Records

19. Packing Records

20. Batch Packaging Records

21. Batch Processing Records

22. Standard Operating Procedures (SOPs) and Records, regarding

23. Reference Samples

24. Reprocessing and Recoveries

25. Distribution records

26. Validation and process validation

27. Product Recalls

28. Complaints and Adverse Reactions

29. Site Master File

 Objective

CGMP provides 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.

 GENERAL REQUIREMENTS

• Location and surroundings

• Buildings and premises
• Water System.
• Disposal of waste
 WAREHOUSING AREA

Adequate areas shall be designed to allow sufficient and orderly

warehousing of various categories of materials and products like

starting and packaging materials, intermediates, bulk and

finished products, products in quarantine, released, rejected,

returned or recalled, machine and equipment spare parts and

change items.
 PRODUCTION AREA
• The production area shall be designed to allow the production preferably
in uni-flow and with logical sequence of operations.
• In order to avoid the risk of corss-contamination, separate dedicated and
self- contained facilities shall be made available for the production of
sensitive pharmaceutical products like penicillin or biological
preparations with live micro-organisms. Separate dedicated facilities shall
be provided for the manufacture of contamination causing and potent
products such as Beta-Lactum, Sex Hormones and Cytotoxic substances.
• Working and in-process space shall be adequate to permit orderly and
logical positioning of equipment and materials and movement of
personnel to avoid cross- contamination and to minimize risk of omission
or wrong application of any manufacturing and control measures.
• Pipe-work, electrical fittings, ventilation openings and similar service
lines shall be designed, fixed and constructed to avoid accumulation of
dust]. Service lines shall preferably be identified by colours and the
nature of the supply and direction of the flow shall be marked/indicated.
 ANCILLARY AREAS
• Rest and refreshment rooms shall be separate from other areas. These areas shall
not lead directly to the manufacturing and storage areas.

• Facilities for changing, storing clothes and for washing and toilet purposes shall be
easily accessible and adequate for the number of users. Toilets, separate for males
and females, shall not be directly connected with production or storage areas. There
shall be written instructions for cleaning and disinfection of such areas.

• Maintenance workshops shall be separate and away from production areas.

Whenever spares, changed parts and tools are stored in the production area, these
shall be kept in dedicated rooms or lockers. Tools and spare parts for use in sterile
areas shall be disinfected before these are carried inside the production areas.

• Areas housing animals shall be isolated from other areas. The other requirements
regarding animal houses shall be those as prescribed in rule 150-C(3) of the Drugs
and Cosmetics Rules, 1945 which shall be adopted for production purposes.
 QUALITY CONTROL AREA

• Quality Control Laboratories shall be independent of the

production areas. Separate areas shall be provided each for
physico-chemical, biological, microbiological or radio-isotope
analysis. Separate instrument room with adequate area shall
be provided for sensitive and sophisticated instruments
employed for analysis.
• Sample Management: Standards, Samples, etc.
 PERSONNEL
• The manufacture shall be conducted under the direct supervision of competent
technical staff with prescribed qualifications and practical experience in the
relevant dosage form 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.
• 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
followed strictly.
• umber 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.
 HEALTH, CLOTHING AND SANITATION OF WORKERS
• The personnel handling Beta-lactum antibiotics shall be tested for
Penicillin sensitivity before employment and those handling sex
hormones, cytotoxic substances and other potent drugs shall be
periodically examined for adverse effects. These personnel should be
moved out of these sections (except in dedicated facilities), by rotation,
as a health safeguard.
• Prior to employment, all personnel, shall undergo medical examination
including eye examination, and shall be free from Tuberculosis, skin and
other communicable or contagious diseases.
• All persons prior to and during employment shall be trained in practices
which ensure personnel hygiene. A high level of personal hygiene shall
be observed by all those engaged in the manufacturing processes.
• All employees shall be instructed to report about their illness or
abnormal health condition to their immediate supervisor so that
appropriate action can be taken.
 MANUFACTURING OPERATIONS AND CONTROL
• All manufacturing operations shall be carried out under the
supervision of technical staff approved by the Licensing Authority.
• The contents of all vessels and containers used in manufacture
and storage during the various manufacturing stages shall be
conspicuously labelled with the name of the product, batch
number, batch size and stage of manufacture. Each label should
be initialled and dt. by the authorised technical staff.
• Precautions against mix-up and cross-contamination
• Line Clearance
• The licensee shall ensure processing of sensitive drugs like Beta-
Lactum antibiotics, sex hormones and cytotoxic substances in
segregated areas or isolated production areas within the building
with independent air-handling unit and proper pressure
differentials.
 SANITATION IN THE MANUFACTURING PREMISES

• The manufacturing premises shall be cleaned and maintained

in an orderly manner, so that it is free from accumulated
waste, dust, debris and other similar material. A validt.
cleaning procedure shall be maintained.
• A routine sanitation program shall be drawn up and observed,
which shall be properly recorded
 RAW MATERIALS

• The licensee shall keep an inventory of all raw materials to be

used at any stage of manufacture of drugs and maintain
records.
• All incoming materials shall be quarantined immediately after
receipt or processing.
• All incoming materials shall be purchased from approved
sources under valid purchase vouchers. Wherever possible,
raw materials should be purchased directly from the
producers.
• If a single delivery of material is made up of different batches,
each batch shall be considered as a separate batch for
sampling, testing and release.
 EQUIPMENT
• Equipment shall be located, designed, constructed, adapted and
maintained to suit the operations to be carried out.

• 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.

• Defective equipment shall be removed from production and

Quality Control areas or appropriately labelled.
 DOCUMENTATION AND RECORDS

• Its aim is to define the specifications for all materials, method

of manufacture and control, to ensure that all personnel
concerned with manufacture know the information necessary
to decide whether or not to release a batch of a drug for sale
and to provide an audit trail that shall permit investigation of
the history of any suspected defective batch.
• Documents shall be approved, signed and dt. by appropriate
and authorized persons.
 LABELS AND OTHER PRINTED MATERIALS
• All containers and equipment shall bear appropriate labels.
Different colour coded labels shall be used to indicate the
status of a product (for example under test, approved, passed,
rejected).
 QUALITY ASSURANCE

• This is a wide-ranging concept concerning all matters that

individually or collectively influence the quality of a product. It
is the totality of the arrangements made with the object of
ensuring that products are of the quality required for their
intended use.
 SELF INSPECTION AND QUALITY AUDIT
• It may be useful to constitute a self-inspection team
supplemented with a quality audit procedure for assessment
of all or part of a system with the specific purpose of
improving it.
 QUALITY CONTROL SYSTEM

• Quality control shall be concerned with sampling,

specifications, testing, documentation, release procedures
which ensure that the necessary and relevant tests are
actually carried and that the materials are not released for
use, nor products released for sale or supply until their quality
has been judged to be satisfactory.
 SPECIFICATION
For raw materials and packaging materials. - They shall include-
(a) the designated name and internal code reference; (b)
reference, if any, to a pharmacopoeial monograph;
(c) qualitative and quantitative requirements with acceptance
limits;
(d) name and address of manufacturer or supplier and original
manufacturer of the material;
(e) specimen of printed material;
(f) directions for sampling and testing or reference to
procedures; (g) storage conditions; and
(h) maximum period of storage before re-testing.
 MASTER FORMULA RECORDS

There shall be Master Formula records relating to all manufacturing procedures for each
product and batch size to be manufactured. These shall be prepared and endorsed by the
competent technical staff i.e. head of production and quality control.

(a) the name of the product together with product reference code relating to its specifications;
(b) the patent or proprietary name of the product along with the generic name, a description
of the dosage form, strength, composition of the product and batch size;
(c) name, quantity, and reference number of all the starting materials to be used. Mention
shall be made of any substance that may ‗disappear‘ in the course of processing.
(d) a statement of the expected final yield with the acceptable limits, and of relevant
intermediate yields, where applicable.
(e) a statement of the processing location and the principal equipment to be used.
(f) the methods, or reference to the methods, to be used for preparing the critical equipments
including cleaning, assembling, calibrating, sterilizing;
(g) detailed stepwise processing instructions and the time taken for each step; (h) the
instructions for in-process control with their limits;
(i) the requirements for storage conditions of the products, including the container, labelling
and special storage conditions where applicable;
(j) any special precautions to be observed; (k) packing details and specimen labels.
 BATCH PACKING RECORDS
• A batch packaging record shall be kept for each batch or part
batch processed. It shall be based on the relevant parts of the
packaging instructions, and the method of preparation of such
records shall be designed to avoid transcription errors.
 BATCH PROCESSING RECORDS
• There shall be Batch Processing Record for each product. It
shall be based on the relevant parts of the currently approved
Master Formula. The method of preparation of such records
included in the Master Formula shall be designed to avoid
transcription errors.
 STANDARD OPERATING
PROCEDURES (SOPS) AND
RECORDS, REGARDING

• Receipt of materials
• Sampling
• Batch Numbering
• Testing
• Records of analysis
 REFERENCE SAMPLES

• Each lot of every active ingredient, in a quantity sufficient to

carry out all the tests, except sterility and pyrogens/Bacterial
Endotoxin Test, shall be retained for a period of 3 months after
the date of expiry of the last batch produced from that active
ingredient.
• Samples of finished formulations shall be stored in the same
or simulated containers in which the drug has been actually
marketed.
 REPROCESSING AND RECOVERIES

• Where reprocessing is necessary, written procedures shall be

established and approved by the Quality Assurance
Department that shall specify the conditions and limitations of
repeating chemical reactions. Such reprocessing shall be
validt..
• If the product batch has to be reprocessed, the procedure
shall be authorized and recorded. An investigation shall be
carried out into the causes necessitating re- processing and
appropriate corrective measures shall be taken for prevention
of recurrence. Re-processed batch shall be subjected to
stability evaluation.
 DISTRIBUTION RECORDS
• Prior to distribution or dispatch of given batch of a drug, it
shall be ensured that the batch has been duly tested,
approved and released by the quality control personnel.
 VALIDATION AND PROCESS VALIDATION

• Validation studies shall be an essential part of Good

Manufacturing Practices and shall be conducted as per the
pre-defined protocols. These shall include validation of
processing, testing and cleaning procedures.
 PRODUCT RECALLS
• A prompt and effective product recall system of defective
products shall be devised for timely information of all
concerned stockists, wholesalers, suppliers, upto the retail
level within the shortest period. The licensee may make use of
both print and electronic media in this regard.
 COMPLAINTS AND ADVERSE REACTIONS
• All complaints thereof concerning product quality shall be
carefully reviewed and recorded according to written
procedures. Each complaint shall be investigated/evaluated by
the designated personnel of the company and records of
investigation and remedial action taken thereof shall be
maintained.
 SITE MASTER FILE
• The licensee shall prepare a succinct document in the form of
Site Master File‘ containing specific and factual Good
Manufacturing Practices about the production and/or control
of pharmaceutical manufacturing preparations carried out at
the licensed premises.
THANK YOU…