regulatory requirements for manufacturing information and formula

REGULATORY REQUIREMENTS FOR MANUFACTURING INFORMATION AND MANUFACTURING FORMULA: 

REGULATORY REQUIREMENTS FOR MANUFACTURING INFORMATION AND MANUFACTURING FORMULA Presented by: Under the guidance of: GANGADHAR REDDY .V A.MADHUSUDHAN REDDY M.PHARM(Ph.D) 10AB1SO304 A.VISHWANATH M.PHARM,(Ph.D)

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MATERIAL RECEIVING: Receiving records & Written procedures for receipt shall be followed. All incoming materials shall be purchased from approved sources under valid purchase vouchers. (if possible, directly from the producers). All incoming materials receipt shall be checked to ensure that the consignment corresponds to the order placed. (FIFE/FIFO Principle). Received containers are de-dusted /de-cartooned by air blowers and vacuum cleaners in de-dusting area and these are carried to the warehousing area which shall protect materials & products from adverse weather conditions.

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IDENTIFICATION: There shall be written procedures for identification. Examine each consignment on receipt. Check each container for integrity of package and seal. Visual Identification examined for appropriate labeling. Damaged containers shall be identified, recorded and segregated.

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QUARANTINE: All incoming materials shall be quarantined immediately after receipt and shall be stored under appropriate conditions. Raw materials shall be appropriately labeled (Quarantine label). Label shall be clearly marked with the following information. Designated name of the product, internal code ref & analytical ref.no etc. Mfg’s name, address & batch no. Mfg, date, Exp date, retest date

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STORAGE: Proper racks & platforms shall be provided for storage of raw materials. suitably spaced to permit cleaning and inspection. Adequate areas shall be designed to allow sufficient and orderly warehousing of various categories of materials & products like starting, packing, intermediate, bulk, finished products in quarantine, released, rejected, returned, Machine &equipment spare parts & change items. Storage areas shall have appropriate house keeping and rodent, pests and vermin control procedures and records maintained. Segregation shall be provided for the storage of rejected, recalled or returned materials or products which are suitably marked & secured.

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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 & secure areas. Adequate fire protection measures shall be provided. Printed packaging materials shall be stored in safe, secure and separate areas. Regular checks are taken against spillage, breakage and leakage of containers. Temp & humidity shall be provided, monitored & recorded.

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Separate sampling area for active raw materials and exicipients which shall be conducted in such a way as to prevent cross-contamination & mix-up. Sampling of sterile materials shall be conducted under aseptic conditions or in dedicated area with in the manufacturing facility. Containers from which samples have been drawn shall be identified. Sample containers shall be identified with the following information. Name of material sampled Lot No. Date of sampling Name of the person who has sampled . SAMPLING :

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Sampling written procedures are maintained and shall be followed. Sampling is done in √n + 1 container and all tests are conducted. Samples from ‘n’ bags are tested for identity. Containers selected for sampling shall be opened, sampled & resealed in a manner designed to prevent contamination. Sterile equipment & aseptic sampling techniques shall be used when necessary. If a container is sampled from top, middle, and bottom, such sample sub-divisions shall not be composite for testing.

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TESTING: There shall be written procedures for testing materials. Tests performed shall be recorded. Each component, containers & closures shall be tested for conformity with all appropriate written specifications for purity, strength, and quality. Components shall be microscopically examined when appropriate. Each lot of component, container, closure liable to contamination with filth, insect, or other adulterant shall be examined against established specifications. Equipment Calibrations, Qualifications ,Validated analytical Methods.

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Q.C APPROVAL: The Q.C unit shall have the responsibility and authority to approve or reject all the materials received including containers closures packaging and labeling materials. Each specifications for raw materials, packing materials shall be approved and maintained by the Q.C dept. Samples of starting materials, packaging materials must be taken by methods and personnel approved by the Q.C. dept. Before releasing a starting or packaging materials for use, the Q.C. manager should ensure that the material have been tested for the conformity with specification for identity, strength, purity and other quality parameters.

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Samples of starting materials, packaging materials must be taken by methods and personnel approved by the Q.C. dept. Before releasing a starting or packaging materials for use, the Q.C. manager should ensure that the material have been tested for the conformity with specification for identity, strength, purity and other quality parameters. Q.A APPROVAL: QA should ensure the arrangements made for the manufacture, supply and use of the correct starting and packaging materials

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MANUFACTURING PROCESS: All mfg. Operations shall be carried out under the supervision of technical staff approved by the licensing authority. There shall be written procedures for production & process control designed to assure that the drug products have identity, strength, quality & purity and shall be followed in the execution of various production and process control functions and shall be documented at the time performance. Major equipment shall be identified by distinctive identification no: or code that shall be recorded in the batch production record. Actual yields and % theoretical yield shall be determined at the conclusion of each appropriate phase of mfg, & processing.

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Actual yields and % theoretical yield shall be determined at the conclusion of each appropriate phase of mfg, & processing. Appropriate written procedures designed to prevent microbial contamination of drug products purporting to be sterile are followed & shall include validation of any sterilization process. Batch production & control records shall be prepared for each batch of drug products produced & shall include complete information relating to production and control of each batch. All the equipments used in the Mfg. Process should be qualified. Approved SOPs for all the activities in the Mfg. Process. The Mfg. Process should be validated and it should be verified at scheduled intervals.

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INPROCESS CONTROL: To assure batch uniformity & integrity of drug products, written procedures shall be established and followed that describe the inprocess controls & tests or examination Inprocess specifications shall be available & should be authenticated. Control procedures such as tablet/capsule weight variation, disintegration time, friability, hardness, clarity, SG, pH of solutions shall be established to monitor the output. During compression of tablets samples shall be taken at regular intervals of not greater than 30 min to ensure that they are being produced incompliance with specified inprocess specification. All inprocess controls shall be recorded.

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BULK TESTING: Specifications for bulk products should be available. Bulk products should be kept under appropriate conditions. Any significant deviation from the expected yield should be recorded and investigated. Samples from Bulk products are tested for complete analysis & the results are recorded and maintained.

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Q.C APPROVAL: The return procedures for production and process controls, including any changes, shall be drafted, reviewed and approved by the QC unit. All drug products, production controlled records, including those for packaging and labeling shall be reviewed and approved by the QC unit. In-process materials shall be tested for identity, strength, quality and purity as appropriate and approved or rejected by the QC unit, during production process.

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Q.A APPROVAL : Any deviation from the written production and process control procedures shall be reported investigated and recorded by the QA dept. Deviations from the established time limits for the completion of each phase of production shall be justified and documented by the QA dept. All the activities involved in the manufacturing process, in-process control and bulk testing shall be approved by the QA dept. All necessary control on intermediate products and any other in-process controls and validations are carried out by the QA dept.

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PACKGING PROCESS: When setting up packaging operations particular attention should be given to minimize risk of cross-contamination, mix-ups or substitutions. Before packaging operations are begun, steps should be taken to ensure that the work area, packaging lines, printing machines & other equipment are cleaned & from any products, materials or documents previously used, if these are not required for current operation. The name & Batch no of the product being handled should be displayed at each packaging station or line. All packaging materials to be used should be checked on delivery to the packaging department for quantity, identity & conformity with the packaging instructions.

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Online control of the product during packaging should include at least checking the following. General appearance of packages Whether packages are complete Whether the correct products & packaged materials are used. Whether any over printing is correct. Correct functioning of line monitors. These shall be batch packaging record for each batch. There shall be written procedures designed to assure that correct labels, labeling & packaging materials are used for drug products. Records of destruction of printed packaging materials.

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FINISHED PRODUCTS SAMPLING: The sample taking should be done in accordance with the approved written procedures that describe the method of sampling. Equipment to be used. The amount of sample to be taken. Type & condition of sample container to be used. Identification of containers sampled. Storage conditions. Reference samples from each batch of finished products should be retained till 1year after the expiry date. Random samples are taken from the finished products batch & examined for complete analysis according to written procedures.

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FINISHED PRODUCTS QUARANTINE: Finished products should be held in quarantine with status label until their final release under conditions established by the manufacturer. Temp. & humidity control are monitored and recorded in the quarantine.

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Q.C APPROVAL: Samples of finished products must be taken by methods and personnel approved by the QC dept. Each specification for final products shall be approved and maintained by QC dept. QC is not only confined to laboratory operations but shall be involved in all decisions concerning the quality of the product. Prior to distribution of given batch of a drug, it shall be ensured that the batch has been duly tested, approved & released by QC personnel. Prior to release, all labels for containers, cartons and boxes and all circulars, inserts& leaflets shall be examined by QC dept.

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Q.A APPROVAL: System of Q.A appropriate to the manufacture of pharmaceutical products shall ensure that the finished product is correctly processed and checked in accordance with established procedures . DISTRIBUTION: Written procedures shall be established & followed describing the distribution of drug products. Distribution records shall contain the name & strength of the product & description of dosage form, name & address of the consignee, date & quantity shipped. Lot or control no of the drug product (for compressed medical gas products), distribution records are not required to contain lot or control nos. Records for distribution shall be maintained in a manner such that finished batch of a product can be traced and complete recall of the batch, if and when necessary.

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Conclusion: Q.A and Q.C guidelines and approval must be considered for every preformulation for better results.

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WWW.ICH.GOV WWW.EMEA.EU.INT hand book of preformulation by SARFARAJ K .NIAZI REFERENCES:

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THANKING “U”