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SCHEDULE M AND SCHEDULE Y

By,Joan Vijetha.RM.Pharm(Pharmaceutics), I year, II sem

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CONTENT• SCHEDULE M• SCHEDULE M I• SCHEDULE M II• SCHEDULE M III• GMP• SCHEDULE Y• CLINICAL TRIALS• SUMMARY• REFERENCES

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SCHEDULE M

GOOD MANUFACTURING PRACTICES AND REQUIRMENTS OF PREMISES, PLANT AND EQIPMENTS FOR PHARMACEUTICAL PRODUCTS

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SCHEDULE M i

REQUIREMENTS OF FACTORY PREMISES FOR MANUFACTURE OF HOMOEOPATHIC PREPARATION.

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SCHEDULE M ii

REQUIREMENT OF FACTORY PREMISES FOR MANUFACTURE OF COSMETICS.

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SCHEDULE M iii

REQUIREMENTS OF FACTORY PREMISES FOR MANUFACTURE OF MEDICAL DEVICES.

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GMP

• GMP is a part of a quality system covering the manufacturing and testing of active pharmaceutical ingredients, diagnostics, pharmaceutical products and medical devices.

• According to rule 71 of drug and cosmetics rules 1945- “THE LICENES SHALL COMPLY WITH THE REQUIRMENTS OF GMP” as laid in schedule M.

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FACTORY PREMISES• The surrounding of the factory should

be free from:–Bad odour.–Bad air.–Water pollutants.– Insects.

• There should be easy disposables of waste and easy access to water and electricity.

• Size should be adequate.

9CLEAN SURROUNDING UNCLEAN SURROUNDING

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BUILDING AND FACILITES• The wall, floor and ceiling should be

made up of non-porous, non-shedding and should be free from cracks and holes.

• Should have adequate space for working and to allows orderly and logical placement of equipment and material to avoid the risk of mix up.

• Cleaning and maintenance facilitation should be good

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LIGHTING, VENTILATION, AIR-FILTRATION,AIR-HEATING AND AIR-COOLING

• Adequate lightening shall be provided to all area.

• The required temperature and humidity should be maintained.

• Air- filtration including pre and particulate matter filters shall be provided.

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REQUIRMENTS FOR STERILE PRODUCTS

• Should be carried in aseptic condition.• High premises of air should be there than other

area.• Laminar flow units should be used.• Periodic monitoring for total particulates.• The light should be mounted into the walls.• Switch's should be placed outside the room.• The mfg. area should be restricted with minimum

no. of persons.• Written procedure must be displayed outside the

wall.

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STORAGE AREA

• Storage area for material designated as “UNDER TEST”, “APPROVED”, “REJECTED”.

• A room for finished product must be provided.

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HEALTH AND CLOTHING

• The persons should be free form any contagious diseases.

• The street cloths should be changed and were clean appropriate cloths.

• Gloves, mask for nostrils and mouths, footer cover, ect,.

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MASTER FORMULA RECORDS

• Name of the product, strength and dosage form.• Description of final container, packaging material

should be labeled.• The identity, quantity and quality of each raw material

to be used.• Description of all vessels, equipment with size used.• Theoretical yield at different stages should be

recorded.• In process quality control test and analysis to be

carried out during each stage of mfg.

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BATCH MANUFACTURING RECORD

• Serial number• Name of the product• Lot\batch size• Lot\batch number• Date• Name of ingredient and quantity used• Actual production and packing particular including the size and

quantity of finished products.• Quality control report for product.• There should not be any overwriting or sticking.• If any sticking is done it should be done diagonally.• Date of release of finished packing for distribution and scale.• Signature of respected staff should be done at each step.

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LABELLING AND PACKING

• Unused coded, spotted label and packaging material shall be destroyed

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SCHEDULE Y

Requirement and guidelines on clinical trails for import and mfg. of new drug.

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Clinical Trial

“Clinical trial” means a systematic study of new drug(s) in human subject(s) to generate data for discovering and / or verifying the clinical, pharmacological and /or adverse effects with the objective of determining safety and / or efficacy of the new drug”.

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Timelines for Regulatory Approvals

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Phase 0 Clinical Trials• This is a recent designation, also called as first in

human trials conducted by US Food And Drug Administration’s.

• This phase is known as micro dosing studies and are designed to speed up the development.

• This include administration of single sub-therapeutic dose to a small group of 10-20 people.

• Does not give information about safety, efficacy, but go/no-go decision can be taken.

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Phase I Clinical Trials

• Phase 1 Clinical Trial(Perform initial human testing in a small group of healthy volunteers)

• In Phase 1 trials the candidate drug is tested in people for the first• time. These studies are usually conducted with about 20 to 100• healthy volunteers. • The main goal of a Phase 1 trial is to discover if the drug is safe in

humans.• Researchers look at the pharmacokinetics of a drug: How is it

absorbed? How is it metabolized and eliminated from the body? They also study the drug’s pharmacodynamics: Does it cause side effects? Does it produce desired effects?

• These closely monitored trials are designed to help researchers determine what the safe dosing range is and if it should move on to further development

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Phase II Clinical Trials

• Phase 2 Clinical Trial(Test in a small group of patients):• In Phase 2 trials researchers evaluate the candidate

drug’s effectiveness in about 100 to 500 patients with the disease or condition under study, and examine the possible short-term side effects (adverse events) and risks associated with the drug.

• They also strive to answer these questions: Is the drug working by the expected mechanism? Does it improve the condition in question?

• Researchers also analyze optimal dose strength and schedules for using the drug.

• If the drug continues to show promise, they prepare for the much larger Phase 3 trials.

• Phase 2 can be done more that one time .

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Phase III Clinical Trials

• Phase 3 Clinical Trial(Test in a large group of patients to show safety and efficacy)

• In Phase 3 trials researchers study the drug candidate in a larger number (about 1,000-5,000) of patients to generate statistically significant data about safety, efficacy and the overall benefit-risk relationship of the drug.

• This phase of research is key in determining whether the drug is safe and effective.

• It also provides the basis for labeling instructions to help ensure proper use of the drug (e.g., information on potential interactions with other medicines).

• Phase 3 trials are both the costliest and longest trials. • During the Phase 3 trial (and even in Phases 1 and 2), researchers

are also conducting many other critical studies, including plans for full scale production and preparation of the complex application required for FDA approval.

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Phase IV Clinical Trials

• Research on a new medicine continues even after approval. As a much larger number of patients begin to use the drug, companies must continue to monitor it carefully and submit periodic reports,including cases of adverse events, to the FDA.

• In addition, the FDA sometimes requires a company to conduct additional studies on an approved drug in “Phase 4” studies. These trials can be set up to evaluate long-term safety or how the new medicine affects a specific subgroup of patients.

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Format of informed consent form for Subjects participating in a clinical trial

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Government is facilitating Clinical trials

No import duty on clinical trial supplies.

Exemption from registration requirements for

clinical trial supplies.

Export of clinical trial related biological specimens

allowed, based on protocol approval.

Exemption from Service Tax on new Drug testing .

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Ethics Committee

At least seven members

Appropriate gender representation on the Ethics Committee.  

EC members who are independent of trial and sponsor should vote / provide opinion in matters related to the study.

Quorum at least 5 members with following representations:

1. Basic medical scientists (preferably one pharmacologist).

2. Clinicians

3. Legal expert

4. Social scientist / Representative of NGO voluntary agency /Philosopher / Ethicist or a similar person

5. Lay person from the community. 

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SUMMARY

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REFERENCE1. SEMINAR ON Regulatory overview of clinical trials in

india by Dr.S.Priestly Vivekkumar, MD,Associate Profess of Dept of Pharmacology, TAGORE MEDICAL COLLEGE.

2. http://www.docstoc.com/docs/966956/Clinical-Trial-Application-Form

3. http://www.docstoc.com/docs/966956/Clinical-Trial-Application-Form

4. Textbook of pharmacuticals by Sanjay K Jain, Vandana Soni, ed-2012,pg-739

5. Drug regulatory affairs by,V Sai Kishre. Ed-2012, pg329-331

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