Manufacture of Drugs

Manufacture of Drugs

Definition: Manufacture in relation to any drug includes any process or part of a process for making, altering, finishing, packing, labelling, breaking up or otherwise treating or adopting any drug with a view to its sale and distribution, but does not include compounding or dispensing of any drug or packing of any drug in ordinary course of retail business.

Manufacture of drugs is a blend of art and science, to be achieved strictly in accordance with the provisions of Good Manufacturing Practices (GMP). A person who is interested in starting manufacturing of drugs is required to fulfill several conditions laid down in DCA and Rules. The conditions to be fulfilled before licence is granted are collectively called as "Conditions Precedent" and conditions that are required to be fulfilled after the licence is obtained for manufacturing are called "Conditions Subsequent". The Licensing Authority is both in States and at Central Government. The Central Government is empowered to prohibit manufacturing and sale of any drug formulation in public interest.

Licences are required for the manufacturing of following categories of drugs.

1. Manufacturing of drugs belonging to Schedules C and C (I)

2. Manufacturing of drugs belonging to Schedule X

3. Manufacturing of drugs belonging to Schedules C, C (I) and X

4. Manufacturing of drugs other than Schedule C, C, and X

5. Manufacturing of drugs for examination, test or analysis

6. Loan licences

7. Licence for Repacking

The following categories of drugs and cosmetics are prohibited to be manufactured or sold in our country.

1. Any drug or cosmetic which is substandard, misbranded, adulterated or spurious.

2. Any patent or proprietory medicine without clear indication of ingredients.

3. Any drug claiming for accurate cure or prevention of diseases listed in Schedule].

4. Any manufacturing of formulation containing drug or cosmetic which has been imported into our country in contravention to the provisions of the Act and Rules.

5. Manufacturing for sale of any drug or cosmetic containing any harmful ingredient.

6. Manufacturing for sale of any drug or cosmetic in contravention to the provisions of the Act and Rules, provided that manufacture of small quantities of any drug for the purpose of examination, test or analysis is permitted, subject to prescribed conditions.

Separate applications for separate licences for more than one premises of manufacture are required to be made.

(A) Manufacturing of Drugs other than Schedules C and C (1)

Application for grant of licence or renewal is made in Form 24. The licence is issued by Licensing Authority in Form 25.

I - Conditions for grant of Licence are as follows:

1. Competent Staff: (i) A graduate in Pharmacy/Pharmaceutical Chemistry with a minimum of 18 months of experience after graduation. The duration may be reduced by 6 months, if the applicant has undergone training during graduation. or (ii)A graduate in Science with Chemistry as a principal subject and with 3 years of manufacturing experience after graduation or (iii) A graduate in Chemical Engineering or Chemical Technology or Medicine with 3 years of manufacturing experience after graduation or (iv) holding equivalent foreign qualification.

For disinfectant fluids. insecticides, liquid paraffin, non-chemical contraceptives, surgical dressings, medicinal gases, plaster of paris, only adequate experience in manufacturing is required and no specific qualification is mentioned

2. Factory premises: As per Schedule' M' with regard to premises, space, plant and equipment.

3. Separate facilities for analysis of raw materials and finished formulations

There should be separate head of department for analysis and manufacturing sections. Head of the testing and analytical department should be a graduate in Medicine/Pharmacy/Pharmaceutical Chemistry/Science with adequate experience in analysis.

4. There should be adequate arrangement of storage of raw materials and finished products.

5. While applying for licence to manufacture patent or proprietary medicines, it is required to submit evidence justifying therapeutic claims of the product, its stability and safety.

II. Conditions to be fulfilled after getting a licence:

1. The manufacturer should always maintain adequate staff, sufficient premises and equipment.

2. The manufacturing records, records for raw material and analysis and other operational records should be maintained as per Schedule 'U'.

3. The licensee should own an analytical laboratory or get tested the samples analysed in an approved analytical laboratory.

The records for analysis are required to be maintained for a period of 5 years from date of manufacturing. The records are both for manufacturing and for finished product.

4. The manufacturer should allow the Inspector to inspect the premises, manufacturing process, analytical procedures, and withdraw the samples. The samples may be provided on demand and entire protocol of manufacturing should be made available when asked for. The manufacturer should also withdraw the batch manufactured by him if directed to do so by the Controlling Authority.

5. The manufacturer should comply with all the requirements of the Act and Rules thereunder.

6. The manufacturer should maintain the Inspection Book.

7. Samples with expiry date should be maintained for 6 months after expiry date. For other categories, the samples should be maintained for 3 years from the date of manufacturing. Twice the lot of reference samples should be maintained. The quantity maintained should be sufficiently available for analysis.

8. Any change in the staff structure especially, technical staff should be reported to Licencing Authority.

9. Any major structural change in the premises should be done with the permission of Licencing Authority

10. The manufacturer should forward all the sales records to the Controlling Authority.

[B] Manufacture of Drugs for Testing, Analysis or Examination

If the manufacturer does not hold separate licence for test, analysis or examination, the licence is obtained in Form 29. The provisions relating prohibition of manufacturing of certain drugs do not apply for such manufacturing meant for test or analysis. The validity of the licence is for I year. The manufactured drugs should be kept in containers bearing appropriate label indicating the purpose of test or analysis. When the material is supplied to other manufacturer, the label stating the name and address of manufacturer, scientific name of the drug, licence number, date of manufacture, etc., should be provided.

The manufacturer should allow the Inspector to inspect the premises, manufacturing, and analytical records and withdraw the samples if required for analysis. The manufacturer should comply with the provisions of the Act and Rules. The manufacturer should maintain an Inspection Book and the same be shown to the Inspector.

[C] Manufacturing of New Drugs

In addition to provisions for manufacture of drugs, there should be documentary evidence for qual ity, purity, therapeutic trials of new drugs and evidence for approval under schedule 'Y' (Clinical trials).

[D] Loan Licences

For drugs other than Schedules C, (I) and X, loan licences can be given. A qualified person can make use of approved facilities of manufacturing provided by any other person and obtain a loan licence for manufacture of drugs other than Schedules C, C (I) and X. The licensee in such cases should convice the Licensing Authority about the availability of the infrastructure on loan from approved manufacturer, and also be convinced about the need to grant such a loan licence.

All the conditions of GMP in Schedule 'M' are required to be fulfilled. Manufacturing Records should be maintained for 5 years. In case of drugs with date of expiry, the records should be maintained for 2 years. Application for grant or renewal of loan licence is made in Form 24-A. The licence is issued by Licensing Authority in Form 25-A, which is valid for I year.

[E] Repacking licence

It is issued for drugs other than Schedules C, C₁ and X, subject to fulfillment of conditions. The application is made for grant or renewal of licence in Form 24-B. The licence is issued by Licensing Authority after inspection in Form 25-B.

There should be adequate arrangement for testing of samples. The licence should always be displaced at premises of repacking. The factory primises for repacking should comply with provisions of Schedule M. Hygienic conditions of working should always be maintained. Adequate staff should be appointed and any change in staff structure should be immediately informed to Controlling Authority.

The Competent person eligible to get Repacking Licence is -

1. Diploma in pharmacy or Registered pharmacist

2. Intermediate with Chemistry as a subject

3. Matriculation with 4 years of experience in manufacture, dispensing or repacking of drugs.

The licence is valid till 3st December every year and required to be renewed. There should be separate application for separate licence.

The container or package of repacked drug should bear on its label the words - "Rpg.Lic.No". The Repacking Licence is given to the competent persons for the bulk drugs or drug formulations procured in large quantities from manufacturer directly and required to be sold in small quantities.

[F] Manufacture of Drugs under Scheaules C and C (1) and Drugs specified in Schedules C, C (1) and X

Application for grant or renewal of a licence is made for Schedules C and C (1) drugs in Form-27 and for Schedules C, C (1) and X in  Form 27-B. The licence is issued in Form-28 for manufacture of Schedules C and C (1) drugs and in Form 28-B for drugs under Schedules C, C (I) and X.

1. The conditions stipulated in Schedule 'M' should be met with. The requirements of space, plant, equipment, etc., should be as per Schedule M.

2. The testing strength or quality strength of the manufacturing un it should be assessed. There should be a qualified independent head for analytical wing including for analysis of Schedules C and C (1) drugs.

3. The competent technical persons should be available with one of the following qualifications.

(i) A graduate in Pharmacy/Pharmaceutical Chemistry with 18 months of experience after graduation in manufacturing drugs to which licence applies. Six months of mandatory training after graduation can form part of this total training of 18 months.

or

A graduate in Science with Chemistry or Microbiology as major subject with a minimum of 3 years of experience after graduation in the manufacture of drugs to which this licence applies.

or

A foreign equivalent qualification or an expert in manufacturing before 29^th June, 1957.

For manufacture of veterinary Scheduled drug formulations, a graduate in Medicine/Veterinary Science/General Science/ Pharmacy with minimum 3 years experience in manufacture of biological products.

4. There should be facilities available for storage of drugs. Sufficient precaution should be taken for preserving the properties of manufactured drugs.

5. Records of manufacturing should be maintained as per Schedule 'U'. Records of test, analysis and examination and batch wise records are required to be maintained. All records should be kept for a period of 2 years from the date of expiry of drug. In other cases, with no expiry date, the records should be kept for 5 years from the date of manufacturing.

6. The manufacturer should allow the Inspector or the representative of Controlling Authority and Licensing authority to visit manufacturing premises with or without notice.

7. The manufacturer should report to the Licensing Authority any changes in staff or any material changes.

8. The licensee should furnish the sample of drugs to the Inspector when asked for purpose of analysis. He should not sell the drug if asked to do so by Controlling Authority and withdraw the drug already sold from the market on direction from the Authority

9. The licensee should maintain the Inspection Book to enable the Inspector to record his observations.