Short Notes on Pharma

Note: 51

Color Added in Uncoated Drugs :

1. If a drug manufacturer applies to manufacture uncoated tablets with color in the formulation, the SLA grants permission either with the words "approved color added" or by specifying the name of the approved color.
2. If the manufacturer fails to add the color mentioned in the formulation, the drug will be classified as a misbranded product.

3. Therefore, while issuing permission, care must be taken to review the stability data of the applied items to ensure the firm has mentioned the color in the formulation.

Must read:

Key Notes on Revised Schedule M: Compilation

Guidance documents for industry 

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 50

Colors Added in Drugs :

Rule: 127

127(1) :
If color is added to the drugs, it must be from the approved list mentioned in the Drugs Act.

127(2) :
The label of the drug shall indicate the common name of the color.

Disinfectants :
In the case of disinfectants, additional colors are mentioned separately or in IS 4707 (part 1) (GSR 625 (E) dated 10.8.22).

Capsule :
127(2) :

Notification :
GSR 1186 (E) Dated 7.12.18.

For gelatine capsules, there is no need to mention the colors of the shells (shells contain approved colors).

pellets:

The name of the color should be mentioned on the label of the drugs, as per Rule 127 of the Drug Act.

Key Notes on Revised Schedule M: Compilation

Guidance documents for industry 

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 49

Medicinal oxygen :

1. Medical oxygen is categorized as "drug" under the ambit of Sect. 3(b)(i) of the Drugs and Cosmetics Act, 1940.

2. Medicinal oxygen is produced in an industrial process complying with Schedule M.

3.The Industrial grade oxygen is not suitable for medical use.

4.The Medical oxygen cylinders are distinct from the industrial oxygen cylinders in respect to their sizes and the color of the cylinder.

5. The empty cylinder has to be serviced periodically to ensure compliance.

Key Notes on Revised Schedule M: Compilation

Guidance documents for industry 

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 48

Expired drugs :

1. This matter was discussed earlier in 58th DCC meeting held on 14.07.2020 regarding the disposal of unused/expired medicine.

2. Sub-committee was formed to examine the issue.

3. The sub-committee has submitted its report.

4. The report of the sub-committee, along with the guidance document on safe disposal of unused / expired medicine was deliberated in detail by the DCC meeting.

5. The DCC agreed in principle with the report of the sub-committee and the guidance document and recommended that the sub-committee may also look into the procedures mentioned under the draft guidance document related to disposal of expired/ unused medicine by the general public before finalization.

Guidance documents for industry 

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Notes : 47

Microscope : Medical Devices

1. Microscope is classified as Microscope by the DCGI office on 25.10.2023, and same has been classified under Class A.

2. It was classified under in-vitro diagnostics medical devices under MDR, 2017.

3. Category is microbiology.

4. On going through the intended use, it is covered under the definition of Non-Sterile & Non measurable notification issued by the GOI.

5. Hence, no license is required under MDR, 2017, and only registration is required on the Sugam portal by the firm.

Procedure to obtain license for manufacturing of Medical Devices

Registration for sale of Medical Devices: Procedure and conditions

Guidance documents for industry 

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 46

Sterile Products :
Sterile Drug Solutions (Not for Injection)

1. These are sterile drugs.

2. They are not intended for injection.

3. The pack size may be up to 3000 ml.

4. These must be manufactured in a sterile section, adhering to all the requirements for parenteral preparations.

5. This product does not fall under the category of Large Volume Parenterals (LVP) or Small Volume Parenterals (SVP).

6. It should be manufactured in accordance with Part 1-A of Schedule M.

7. Specific requirements for the manufacture of sterile products include parenteral (small and large volume) and sterile ophthalmic preparations.

8. Product permission must be obtained on Form-28.

Guidance documents for industry 

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 45

Pack Sizes of Drugs (Cream Formulations):

1. No specific pack size has been specified for creams under rule 105 of the Drugs and Cosmetics Act.

2. Drug manufacturers can manufacture cream dosage form of any pack size supported by stability studies.

3. For 'Ciclopiroxolamine Cream' only one pack size of 30 gm has been specified by
Schedule P1 (Rule 109) of Drugs and Cosmetics Act and Rules.

Schedule P1

Guidance documents for industry 

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 44

Revised Schedule M: Drugs Recall:

1. Voluntary recalls are allowed as per the law and WHO guidelines.

2. Depending on the findings, recalls can be initiated from wholesale and retail levels. The LA may be informed.

3. Written procedures must be in place to recall drugs at any point, following an established and effective recall process in adherence to the SOP.

4. Voluntary recalls should follow the procedure outlined in the CDSCO guidance.

5.As per the revised Schedule M, it is now mandatory.

CDSCO Guidelines on Drug Recall

Guidance documents for industry 

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 43

Retention of Drug Manufacturing License

1. ‘Renewal’ of Drugs Manufacturing Licenses has been omitted since October 27, 2017 vides notification number GSR 1337(E) Dated 27.10.2017 issued by the Govt. of India.

2. In place of “Renewal” the term "Retention" has been introduced.

3. “Retention” is applicable for the continuity of following categories of licenses:

• Allopathic API/formulations manufacturing License
• Testing laboratories License
• Repacking License
• Cosmetic Manufacturing License
• Medical devices Manufacturing License
• Sale License

4. “Renewal” is still applicable for the continuity of following categories of licenses:

• License to operate Blood Centres
• Homoeopathic Manufacturing License

Guidance documents for industry 

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 42

Reference Sample:

Rule : 74(I)

1. In the Drugs Act, the term "reference samples" is used, not "control samples.".

2. Reference samples must be retained for 3 months after their expiry date.

Guidance documents for industry 

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 41

Ketamine: Regulations

1. Ketamine has been categorized as Psychotropic Substance and included in the list of Psychotropic Substances at Sr. No. 11oA vide notification no. S.O. 311(E) dated 10.02.2011 issued by Department of Revenue, Ministry of Finance, Government of India.

2. Ketamine has also been declared Scheduled Drug and inserted in Schedule X of Drugs and Cosmetics Rules, 1940 vide notification no. GSR 724(E) dated 07.11.2013 by Department of Health, Ministry of Health and Family Welfare, Government of India.

3. Both label warnings i.e. warning for Psychotropic Substances as well as warning for Schedule X Drugs are mandatory to be printed on the label of this drug.

4. Ketamine is not an Essential Narcotic Drug (END).

5. ‘NRx’ should be printed in red colour on the top left corner of the label of drug.

6. License under provisions of Schedule X is mandatory for manufacturing and sale of Ketamine Drug.

7. Doctors can purchase this drug to be used for their patients from a licensed Chemist shop.

Also read: Ketamine: Understanding its Classification and Regulations in India

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 40

Requirement of Area as per Schedule M:

(Basic area + Ancillary area)

1. Tablets:
60 + 20 = 80 square meters

2. Coating:
30 + 10 = 40 square meters

3. Capsules:
25 + 10 = 35 square meters

4. Oral Preparations:
30 + 10 = 40 square meters

5. External Preparations:
30 + 10 = 40 square meters

6. SVP (Small Volume Parenterals):
100 + 50 = 150 square meters

The above-mentioned Area for Separate Categories:

• General
• Beta-lactam
• Hormonal
• Cytotoxic

Read for more details on Area: Click here

Download requirement of Area chart: Click here

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 38

Sterility Testing :

1. As per the Drugs and Cosmetics Act and Rules, Parametric release of drugs is not permitted in India.
2. However, to expedite the testing process (as sterility testing typically takes 14 days), alternative testing methods specified by the Indian Pharmacopeia (IP) can be used but only after seeking approval of the State Licensing Authorities (SLA).
3. In case of any dispute, only the standard 14 days sterility testing method will be accepted.

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 37

Schedule H drugs:

1. All the Drugs notified under Schedule H of Drugs and Cosmetics Act and Rules are known as ‘Schedule H Drugs’ and ‘Schedule H Drug Warning’ as required under Act must be printed on the label of these drugs.
2. Till date 543 drugs have been notified as Schedule H drugs.
3. For External Preparations, only drugs containing antibiotics and/or steroids can be labeled as ‘Schedule H drug’.
4. Eye drops, ear drops and nasal drops containing antibiotics and/or steroids must be labeled as ‘Schedule H drug’.
5. Following categories of drugs need not to be labeled as Schedule H drugs:
   • Veterinary drugs
   • Injections
   • External Preparations, if do not contain antibiotics and/or steroids.
   • Eye drops, ear drop and nasal drops, if do not contain antibiotics and/or steroids.

Also read: 

Schedules: All types of Drugs

Schedules: All types of Cosmetic

Schedules: All types of Medical Devices

Schedules: All types of Clinical Trials

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 36

Revised Schedule M

Tablets and Capsules : Part 8

1. Enclosed dust control manufacturing systems shall be provided for processes such as sieving, granulation, paste mixing, and punching.

2. Air conditioning shall be provided wherever necessary. (The area should be air-conditioned.)

3. Effective air extraction shall be ensured through the use of AHUs.

4. Filters shall be installed to retain dust and protect both the factory and the local environment.

5. The use of metal detectors is recommended.

6. Pressure differentials between rooms shall be regularly monitored.

7. The pressure cascade shall ensure that the airflow direction is from the clean corridor into the cubicles, resulting in dust containment.

8. The corridor shall be maintained at a higher pressure than the cubicles, and the cubicles at a higher pressure than atmospheric pressure.

9. Highly potent products shall be manufactured under a pressure cascade regime that is negative relative to atmospheric pressure.

10. Pressure control and monitoring devices shall be calibrated and qualified.

11. Pressure control devices shall be linked to an alarm system.

12. Airlocks are important components for setting up and maintaining pressure cascade systems:
(a) Cascade Airlock: Higher pressure on one side of the airlock and lower pressure on the other side.
(b) Sink Airlock: Lower pressure inside the airlock and higher pressure on both outer sides.
(c) Bubble Airlock: Higher pressure inside the airlock and lower pressure on both outer sides.

13. Doors shall open toward the high-pressure side.

14. Airlocks shall be interlocked.

15. Color-coded gauges may be helpful.

16. Pass Boxes (PB) can be used to separate two different zones.

17. Temperature and relative humidity shall be controlled, monitored, and recorded.

18. Maximum and minimum room temperatures and relative humidity levels shall be appropriate.

19. Exhaust air discharge points on pharmaceutical equipment and facilities, such as fluid bed dryers, tablet-coating equipment, and dust extraction systems, which carry heavy dust loads, shall be equipped with adequate filtration to prevent contamination of the ambient air.

20. For powders that are not highly potent, final filters on dust exhaust systems shall be fine dust filters with a classification of 5 µm.

21. HEPA filters may be located within the air handling unit or placed terminally.

22. Airlocks, such as personnel airlocks (PAL), material airlocks (MAL), change rooms, and passages, shall be provided to ensure protection between areas of differing cleanliness.

23. These airlocks shall have appropriate supply and extract air systems.

24. Detailed diagrams depicting pressure cascades, airflow directions, and flow routes for personnel and materials shall be prepared and maintained.

25. Filter bags fitted to fluid-bed dryers shall not be reused for different products without being thoroughly washed between uses.

26. For certain highly potent or sensitizing products, product-specific bags shall be used.

27. Air entering the dryer shall be filtered.

28. Accurate and calibrated weighing equipment shall be readily available and used for in-process monitoring of tablet weight variations.

29. Tablets shall be de-dusted, preferably using an automatic device, and monitored for the presence of foreign materials and other defects.

Also Read:

Key Notes on Revised Schedule M: Must read

Guidance documents for industry 

Guidance documents for industry 

AHUs, Air Types, Air Changes and their Functions in Pharma Industry

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 35

Waste Materials Management as per Revised Schedule M (Point 16):

1. Provision shall be made for the proper and safe storage of waste materials waiting disposal.

2. Toxic and flammable materials must be stored in separate, suitably designed enclosed cupboards.

3. Waste material must not be allowed to accumulate. It should be collected in suitable receptacles and transported to external collection points. Disposal should be carried out safely, hygienically, and at frequent intervals.

4. The disposal of solid, liquid, and gaseous effluents from manufacturing areas must comply with the guidelines of the Environmental Pollution Control Board.

5 Bio-medical waste must be destroyed in accordance with the Bio-Medical Waste (Management and Handling) Rules, 2016.

6.Rodenticides, insecticides, fumigants, and sanitizing agents must not contaminate equipment, starting materials, packaging, in-process materials, or finished products.

Also Read: Guidance documents for industry

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 34

Raw Materials Records:

Records of raw materials are to be maintained as per Schedule M of Para 10.

1. Records of raw materials are to be maintained as per Schedule U.

2. All incoming materials are to be quarantined.

3. APIs are to be received with proper bills and from approved sources.

4. Damaged containers are to be recorded

5. If received materials of the same type are from different batches, each batch is to be tested

6. Label Details :
* Name of product
* Analytical reference no.
* Manufacturer's name
* Manufacturer's batch no.
* Manufacturer's address
* Status of contents (Quarantine, Under Test, Approved, Rejected)
* Manufacturing date
* Expiry date
* Retest date

7. Controlled temperature and humidity are required

8. Containers from which samples have been taken are to be identified.

9. The shelf life of a formulation shall not exceed the expiration date of the raw materials used in its manufacture.

10. Raw material containers should not be kept directly on the floor.

Also Read: Guidance documents for industry

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 33

Medical Devices : Class A (Non sterile & Non-Measurable medical devices).

1. The 91st DTAB meeting was held on August 14, 2024.

2. Agenda Point No. 8.

3. There is Provision of exemption of license to manufacture and import of Class A (Non sterile & Non-Measurable medical devices).

4. The product (at point No. 3) manufacturer should adhere to the quality management system of the 5th Schedule of MDR, 2017.

5. Hence, undertaking stating that the manufacturing facility has complied with the quality system as per the 5th Schedule is required.

6.Therefore, the government proposes to amend rules 19 H and 19J of Chapter 3B of the MDR, 2017, to include quality management system requirements for above said medical devices .

Read or download:

Classification of Medical Devices

Schedules of Medical Devices

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 32

Parenteral Preparations :

1. These products should be sterile and free from:
* Foreign contaminants
* Pyrogens
* Bacterial endotoxins
* Microorganisms

2. Parenteral preparations may be solutions or suspensions.

3 No color should be added to the finished product.

4. Antimicrobial preservatives may be added to multiple-dose drug containers.

5. Preservatives should not be added if the volume to be injected exceeds 15 .

6. Antioxidants may be added if the ingredient is susceptible to oxidative degradation.
Or air may be displayed by nitrogen.

7.Multiple-dose containers should not exceed 10 doses

8. The name of the antimicrobial preservative should be mentioned on the drug label.

9. No parenteral route is permitted for homeopathic and Ayurvedic medicines.

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 31

Injection Section Manufacturing Area Monitoring :

1. HEPA Filters Integrity Testing : Yearly

2. Particulate Counts : Six-monthly

3. Air Change Rates : Six-monthly

4. Air Pressure Differentials: Daily

5. Temperature and Humidity : Daily

6. Microbiological Monitoring : Daily

Read: Guidance documents for industry

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 30

Retention of Allopathic Manufacturing License :

1. With effect from October 27, 2017 term "renewal" of Drugs Manufacturing License (DML) has been omitted.

2. Term "retention" has been introduced in place of term "renewal"

3. Retention describes the ongoing validity of license.

3. No dedicated form has been specified by the Drugs Act to apply retention of DML.

4. Product permissions will be retained if the firm submits retention fee along with item fees before the expiry of license.

5. While submitting application for retention of DML, the firm should consider following points:

• Do not apply for permissions/license for BANNED DRUGS.
• When retention of already approved items applied, the applied items should be based on the current Pharmacopoeial status.
• Rule 124 and the Second Schedule of the Drugs Act mandates that the labeling of drugs should be as per the latest Pharmacopoeial standards.

Read: Guidance documents for industry

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 29

Revised Schedule M - with effect from December 28, 2024

Key points in Part 1: 20 points:

* Pharmaceutical Quality System (PQS)

* Quality Risk Management

* Good Manufacturing Practices for Pharmaceutical Products

* Sanitation and Hygiene

* Qualifications and Validation

* Complaints

* Product Recalls

* Change Control

* Production Under Loan License or Contract and Contract Analysis and Other Activities

* Self-Inspection, Quality Audits, and Suppliers' Audits and Approval

* Personnel

* Training

* Personal Hygiene

* Materials

* Reference Standards

* Waste Materials

* Documents

* Good Practices in Production

* Good Practices in Quality Control

* Computerized Systems

Read: Guidance documents for industry

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 28

Types of facilities for the manufacture of allopathic drugs as per Schedule M :

1. Dedicated separate manufacturing facilities are required to manufacture the following categories of drugs:

- Beta-lactam
- cytotoxic
- Hormonal
- General

2. If a firm inadvertently got permission to manufacture a drug for which separate dedicated facility is required, but the firm has not provided dedicated facility in its manufacturing unit, then the firm should surrender that permission to the Licensing Authority.

3. As per WHO GMP Site Certification, the Beta-lactam section is further divided into the following categories:

* Penicillins
* Cephalosporins
* Carbapenems

Read: Guidance documents for industry

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana