Important short notes for Industry and Regulators

Note: 41

Ketamine: Regulations

1. Ketamine is classified as a psychotropic substance vide notification no. S.O. 311(E) dated 10.02.2011, issued by Ministry . It was declared as a Scheduled X drug vide notification no. GSR 724(E) dated 07.11.2013, issued by Health, Ministry .

4. Labelling :
Both warnings for posychotropic substances and Scheduled X drugs are obligatory to be printed on the label of ketamine.

5. NRx should be printed in red in the top left on the label.

6 Manufacturing and sale licenses are required for ketamine drug under Schedule X.

7. Ketamine is not Essential Narcotics Drugs (END)

8. Doctor can purchase this drug from a licensed chemist shop to administer to their patients.

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:

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

Note: 27

Coating of Drugs:

1. Coating of drugs, i.e., Tablets, Granules, etc. is optional.

2. If India Pharmacopeia monographs a drug is mentioned as a coated drug, then the coating of that drug is mandatory.

3. As per India Pharmacopeia (IP), a drug product may be coated as mentioned in the General Monograph.

4. Only the permitted colors given under rule 127 of Drugs Act and Rules can be used in the coating of drugs.

5. As per rule 127 of Drugs Act and Rules, the common name of the color used in the drug should be indicated on the label of that drug.

Read: Guidance documents for industry

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 26

Rule : 105 of drugs Act.

Pack size of Pediatric Oral Drops.

1. The pack sizes for Pediatric Oral Drops should be 5ml, 10ml, or 15ml only

2. The pack sizes of Liquid Oral Preparations for pediatric use should be 30 ml only.

3. However, the above written provisions of pack sizes are not applicable to vitamins, tonics, cough Preparations, etc.

4. As per Schedule P1 of Drugs Act, the pack size for vitamins in oral drops is 7.5 ml.

Read or download: Schedules for Drugs 

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 25

Pathogen Testing as per Schedule M (8.1)

1. Drugs must be free of pathogens like Salmonella, Escherichia coli, Pseudomonas aeruginosa, etc.

2. This means that drugs, i.e., tablets, capsules, liquid orals, topicals, etc. should be tested for the presence of these pathogens.

3. The manufacturing firm should adopt SOP to ensure the absence of pathogens in all manufactured drugs.

4. The firm should conduct periodic testing for drugs to be free from pathogens.

5. Water used in the preparation of paste during manufacturing procedures should be free from pathogens.

6. The manufacturing area should frequently be monitored/checked for the absence of pathogens.

7. The firm should have a microbiology laboratory for testing of pathogens and validation of area within the drug manufacturing facility.

Read or download: Schedule M

Read or download: Revised Schedule M

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 24

Sex Hormone Drugs :

1. As per the provisions of paragraph 3 of Schedule M of the Drugs Rules, a separate, dedicated facility /  section is required for the manufacture of Sex Hormone Drugs.
2. A license to manufacture these hormone drugs is granted on Form 28 under the Drugs Rules.
3. List of a Hormonal Drugs:

   * Levonorgestrel
   * Ethinylestradiol
   * Drospirenone
   * Norethisterone
   * Allyloestrenol
   * Estradiol Valerate
   * Progesterone
   * Stanozolol
   * Mesterolone
   * Testosterone
   * Cyproterone
   * Dienogest
   * Clomiphene
   * Mesterolone

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 23

Glucometer :

1. Glucose test kits has been notified under the category Clinical Chemistry as Class B in-vitro diagnostics medical devices under the provisions of 4 (2) of MDR, 2017.

2. Glucometer has been notified as a drug under section 3(b)(iv) of the Drugs Act vide Notification number S.O. 5980 (E) dated 03.12.2018 enforced w.e.f. 01.01.2020.

3. Glucometer has also been classified as Class C medical Device vide issued by DCGI file number 29/misc/3/2017-DC(292) dated 15.05.2019.

4. Glucometer is to be regulated under the IVD category.

5.If the Glucometer is to be manufactured with accessories (i.e. glucose testing kit including testing strip, lancet, and alcohol swab) as a single unit / pack, then the firm is required manufacturing license for the glucometer under class C and should mention all accessories in MD Form-9.

6. If the manufacturer has to manufacture glucose testing strips, lancets, and alcohol swabs as a single packaging unit for sale, then license on MD-Form 5 is required.

7. If the manufacturer wants to manufacture glucose strips without a glucometer, then license on Form-MD5 is required.

Also read or download: Latest notification: Medical Devices

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 22

Show cause notice to Manufacturers :

Allopathic drugs and APIs :
Rule 85 (2) of Drugs Rules.

Homeopathic drugs :
Rule 85 (I) (1) of Drugs Rules.

Blood centers :
Rule 122-O of Drugs Rules.

Testing Labs :
Rule 150 (K) of Drugs Rules.

Medical Device :
Rules 30(1) of MDR 2017.

RMI :
Rule 52 P (2) of NDPS Rules

Cosmetic :
Draft rules for insertion of Rule 31A are not yet finalized.

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 21

Labeling of Chlorpheniramine and Phenylephrine drops :

As per the DCGI letter dated 18.12.2023 :

1. The labeling of the above combination has been amended.

2. The drug should not be used in children below the age of 4 years.

3. A warning should be included on the drug labels and package inserts.

4. This order is effective prospectively.

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana

Note: 20

DCGI Letter : Regarding Sub-standard Samples

Directions : 33P

Date : 5.12.2008

1. The DCGI office issued a guideline document for taking action against sub-standard samples under Direction 33P of the Drug Act.

2.Earlier directions were issued in the year 1993.

Also read or download:

• CDSCO Guidelines for taking action on samples declared as Spurious or NSQ
• DCGI circular dt 09-02-2024 Regulatory Guidelines for sampling of drugs, Cosmetics and Medical Devices by Drugs Inspectors of Centre and States

Lalit. Kr. Goel
Deputy State Drugs Controller
FDA Haryana