A REVIEW ARTICLE ON AN EXISTING SCHEDULE M VS REVISED SCHEDULE M

A REVIEW ARTICLE ON AN EXISTING SCHEDULE M VS REVISED SCHEDULE M

Sayantani Dey, Shayari Dutta and Jaydip Ray *

Department of Regulatory Affairs, Guru Nanak Institute of Pharmaceutical Science and Technology, Kolkata, West Bengal, India.

ABSTRACT: Schedule M is considered as an important part in the Drugs and Cosmetics Act 1940, Rules 1945. For making a product with proper quality and effective for the human beings it is necessary to maintain or follow the guidelines of schedule M. Schedule M is considered as the guidelines which talks mostly about Good Manufacturing Practices. Schedule M was first established in the year 2001 and it was divided into Part 1 and Part 2. Then in the year 2018 it was divided into 12 Parts more precisely than first one which was established in the year 2001. Then in the year of 2024 it became more precise, and it was divided into 13 Parts and including the changes introduced in, the revised Schedule M which include introduction of a Pharmaceutical Quality System (PQS), Quality Risk Management (QRM), Product Quality Review (PQR), Qualification and Validation of Equipment, and a Computerized Storage system for all drug products. These revised Schedule M will help in making the product proper and effective to the human beings. The revised Schedule M makes it easy for the identification of the risk and to check whether the product is maintaining quality system or not. The revised Schedule M will make the records of the documentation for future references. Schedule M is a crucial part for all the manufacturing products used by the human. Previous Schedule M doesn’t give much explanation about each topic which creates problems most of the time. It is better to be revised.

Keywords: Guidelines, Computerized, Identification, Qualification, Validation

INTRODUCTION: Schedule M is the set of guidelines or regulations which mainly deals with the good manufacturing practices for the pharmaceutical products ^{1, 2}. It is the part of Drugs and Cosmetics act 1940, rules 1945. It is being followed by all the manufacturers for making a good therapeutic product for the human beings. The products which are made by following the rules or guidelines is effective.

It is a part of quality assurance system which tells that the products are consistently manufactured, and quality standards appropriate to their intended use. The new schedule M has 13 parts. The existing schedule M only focuses on the good manufacturing practices, but the revised schedule M put a special focus on the premises, plants and equipment with the addition GMP requirements.

In addition, they also focus on the Product quality review (PQR), Pharmaceutical quality system (PQS), Quality risk management (QRM), Qualification and validation of equipment and computerized storage system for all products. It also focuses on the risk management and self- inspection. This will help in producing the drug’s safety, quality and efficacy ^{5, 6}

The revised schedule is more specific to the topic and helps in manufacturing a product with good quality, and effective. As we know that schedule M is the vital part and it is followed by the manufacturers minutely ^{3, 4}.

History: Good manufacturing part of Drugs and Cosmetics Act 1940, was first incorporated in Schedule M of the Drugs and Cosmetics Act & Rules, in the year 1988 and the last amendment was done in June, 2005, deals with Good Manufacturing Practices for pharmaceuticals that should be followed by pharmaceutical manufacturing units in India ^{7, 8}. Schedule M guides on Good Manufacturing Practices regarding company premises, quality control system, quality check laboratories, production, cleaning of equipment, housekeeping, cross-contamination, and other related topics.

On the last year of 28^th December 2023, the revised schedule M was implemented which mostly focuses on the quality management system of the pharmaceutical product ^{10, 11}.

Salient Features:

OLD Schedule M: Schedule M was first divided into 2 parts:

Part 1:

• Good Manufacturing practices for the premises and materials.
• It also had a subpart starting from 1A to 1F.

Part II:

• Requirements of Plant and Equipment:
• External Preparations.
• Oral Liquid Preparations
• Tablets
• Powders
• Capsules
• Surgical Dressing
• Ophthalmic Preparations
• Pressurizes and suppositories
• Inhalers and vitrallae
• Repacking of Drugs and Pharmaceutical Chemicals
• Parenteral Preparation

Proposed Schedule M: Schedule M was divided into 12 parts:

Part I: Good Manufacturing Practices for Pharmaceutical Products.

• Part I is completely different.
• This Part I is termed as “Main Principles” & it is mandatory to follow irrespective of product category.
• An Appendix I which deals with requirements of Site Master File.

Part II to Part XII:

• Specified requirements for manufacturing, as per product categories. E.g. Sterile products.
• Oral Solid dosage Forms etc.
• Five new categories are added as compared to existing Schedule M.

Part XIII:

• Requirements of plant and equipment for manufacturing of 11 categories of pharma products.
• This section is similar as of previous schedule M 2001.

New Schdeule M: Good Manufacturing Practices and Requirements of Premises, Plant and Equipment for Pharmaceutical Products

Part I:

• Pharmaceutical Quality system
• Quality Risk Management
• Good Manufacturing practices for pharmaceutical products.
• Sanitation and Hygiene
• Qualification and Validation.
• Complaints and Adverse Reaction
• Product Recall
• Change Control
• Production under loan license or contract and contract analysis and other activities.
• Self-inspection, quality audits and supplier audits and approval
• Personnel
• Premises
• Equipment
• Materials
• Reference standards
• Waste materials.
• Documentation
• Good practices in production
• Good practices in quality control
• Computerized system

Appendix -1: Site master file.

Part II to Part XII:

• Part II- Specific requirements for manufacture of Sterile Products, Small & Large Volume Parentals, Ophthalmic Preparations.
• Part III Specific requirements for manufacture of Hazardous substances such as Sex Hormones, Steroids or Cytotoxic substances (Newly Added).
• Part IV Specific requirements for manufacture of Biological Products (Newly Added).
• Part V Specific requirements for manufacture of Radiopharmaceutical Products (Newly Added).
• Part VI Specific requirements for manufacture of Phytopharmaceutical Products (Newly Added).
• Part VII Specific requirements for manufacture of Investigational Pharmaceutical Products for Clinical Trials in Human (Newly Added).
• Part VII Specific requirements for manufacture of Oral Solid Dosage Forms.
• Part IX Specific requirements for manufacture of Oral Liquids.
• Part X Specific requirements for manufacture of External Preparations.
• Part XI Specific requirements for manufacture of Metered Dose-Inhalers.
• Part XII Specific requirements for manufacture of Active Pharmaceutical Ingredient.

Part XIII:

1. Requirements of Plant and Equipment for External Preparations.
2. Requirements of Plant and Equipment for Oral Liquid Preparations.
3. Requirements of Plant and Equipment for Tablets.
4. Requirements of Plant and Equipment for Powders.
5. Requirements of Plant and Equipment for Capsules.
6. Requirements of Plant and Equipment for Surgical Dressing.
7. Requirements of Plant and Equipment for Ophthalmic Preparations.
8. Requirements of Plant and Equipment for Pessaries and Suppositories.
9. Requirements of Plant and Equipment for Inhalers and Vitrallae.
10. Requirements of Plant and Equipment for Repacking of Drugs and Pharmaceutical Chemicals.
11. Requirements of Plant and Equipment for Parental Preparation.

New Schedule M Principles:

Pharmaceutical Quality System (PQS): It is a part of pharmaceutical Management system in a pharmaceutical Industry. Pharmaceutical quality system should be applied to the product starting from the manufacturing of the product to the dispatch of the product to the market ¹³. In every manufacturing company the senior management responsibility is to implement an effective PQS in the company. The finished product should be checked and confirmed then only they are dispatched. The CAPA (Corrective action and preventive action) should be maintained so that any problem is there with the product then it can be identified by the root cause analysis so that the problem does not occur in the future ¹⁵.

FIG. 1: FLOW CHART OF CAPA PROCESS

There should be also quality risk management for identifying the risk. Any defect, deviations or other problems should be reported, investigated and recorded. The self- inspection or audit should be done in each step so that the mistake can be overcome ¹⁷.

The aim of the Pharmaceutical Quality Management System (QMS) is to guarantee and uphold consistent and superior quality in the manufacturing of pharmaceutical products through an all-encompassing set of guidelines, protocols, and practices ¹⁸.

Quality Risk Management: It is the specific tool to assess the risk or the defects associated with the manufacturing of the product and drug substances. If we can overcome the risks associated with the product then we can provide a quality product ¹⁷.

There is always some danger involved in the production and use of medication (medical) products, including their constituent parts. The whole risk consists of more than just the risk to its quality.

It's critical to realize that good risk-based decision-making throughout the product lifetime ensures that the qualities critical to the medication (or medicinal) product's quality are preserved and that the product continues to be safe and effective ¹⁶.

FIG. 2: FLOW CHART OF RISK IDENTIFICATION PROCESS

Product Quality Review: It is necessary to carry out rolling, periodic, or regular quality reviews of all pharmaceutical items. Check that the quality parameters and product process are consistent. Based on the quality review report, the manufacturer should determine whether re-validation or the relevant CAPA is required. CAPAs must be finished on time and include an ongoing evaluation of their efficacy ¹⁴.

In addition to making sure the data is accurate, the person in charge of product release should make sure the quality review is finished in the allotted time. Every year, product quality reviews must be carried out and recorded ¹³.

Every annual review report must also take into account all of the prior reviews.

The report should address a few of the following topics, but not all of them:

• Examination of the product's raw components and packaging materials.
• Examining the traceability of active ingredients in the supply chain.
• Examination of crucial process controls and final product outcomes a study and inquiry of every batch that didn't match the specified specifications.
• An examination of all modifications made to the procedures or analytical techniques.
• An examination of the filed, approved, or rejected dossier variations.
• An analysis of the stability monitoring program's findings and any unfavorable patterns.

Sanitation and Hygiene: Strict standards of hygiene and sanitation must be followed in all facets of the pharmaceutical manufacturing process. The scope of hygiene and sanitation should include Employees, Facilities, Containers, Production Materials, Equipment and Cleaning and Disinfecting Products. Anything that comes into contact with the merchandise ¹⁵. It is necessary to remove any potential sources of contamination. There should be a sanitization and hygiene program in place. Wash hands with soap and water ¹³. The dress should be clean or else it would cause cross contamination to the product. The personnel who are involved in the manufacturing industry should be free from any kind of diseases.

The Qualification and Validation: The updated schedule M lists more precise requirements than the previous one did. The equipment, instruments, processes, and procedures that the company wants qualified and validated should be identified. There should be a validation master plan in place outlining the essential components of validation and qualification program ¹⁴. It is actually used to establish and proof design Qualification (DQ), installation qualification, performance qualification (PQ) / process, operations qualification (OQ), and qualification (IQ) verification (PV). Re-qualification and re-validation requirements must be specified precisely ¹⁵. The accountability for carrying out validation activities needs to be specified explicitly. Special consideration must be given to the validation of automated systems, analytical test methodologies, and methods for cleaning. It is also playing an important role in manufacturing of the product ¹⁶.

Production under Loan License or Contract and Contract Analysis and Other Activities: One of Schedule M's most significant additions. To prevent quality problems, activities carried out under a specific arrangement and covered by GMP should be precisely defined, agreed upon, and crucially controlled. The following tasks, including but not limited to tech transfer, supply chain, subcontracting validation, batch releasing authorization, changes or changes resulting from incidents or errors, quality control, in-process controls, etc., should be covered by a quality contract or agreement ¹⁹.

Continual the vendor's contract acceptor conducting an audit of the site(s) should be cognizant of all the hazards related to the product, work, or tests that could endanger persons, property, equipment, etc. Competent individuals with the necessary understanding of process technology, analysis, and good manufacturing practices should develop the contract's technical provisions.

Computerised System: Very significant section regarding the regulatory agencies' present strategy. The qualification, validation, review, and data management related to computerized systems are covered in detail in this section. Validation needs to be grounded in the system's complexity, diversity, and criticality. Any modifications to the electronic system must follow a change procedure with upholding and approving each and every record. These documents will show that the system is kept up to date and validated ¹⁸. There must be a backup system in place to ensure that documents are never permanently lost because of failure or collapse of the system. Computerized systems must be equipped with sufficient safeguards against unwanted access or modifications to the data.

Waste Materials: Waste materials must be stored properly and safely in a designated area. It is necessary to properly segregate waste materials from one another. Combustible and toxic products must be stored in appropriately designed, independent, closed cabinets. The removal of solid, liquid, and gaseous effluents and sewage. The manufacturing area must adhere to the specifications of Board for Environment Pollution Control. All biomedical waste needs to be eliminated in accordance with the guidelines of the Biomedical Waste Products. Fumigating agents, insecticides, rodenticides, and sanitizing supplies not allowed to contaminate tools, supplies for starting, materials used in packaging, manufacturing processes, or final goods. Waste materials should be put in the dustbin for the better use.

TABLE 1: COMPARISON BETWEEN SCHEDULE M AND REVISED SCHEDULE M

CONCLUSION: It is concluded that the new or the existing schedule M is very useful for the pharmaceutical industry in manufacturing a product. The existing schedule M is fully explained than the revised schedule M. Existing Schedule M had 12 parts but the new schedule M is 13 parts and it is more precise. As we know that schedule M mostly talks about good manufacturing practices. Existing schedule M doesn’t include the requirements of the radiopharmaceuticals, phyto-pharmaceuticals, investigational Pharmaceutical products used in the clinical trials. Proper schedule m will help in making a good pharmaceutical product along with maintaining a safety, quality and efficacy.

ACKNOWLEDGEMENT: We would like to express our sincere gratitude to the editors and reviewers for their valuable time, expertise, and constructive feedback provided during the review process of this manuscript. Their insightful comments and suggestions have greatly contributed to improving the quality and clarity of the content. We also extend our appreciation to our guide Mr. Jaydip Ray, Assistant Professor, Dept. of Regulatory affairs, Guru Nanak Institute of Pharmaceutical Science and Technology, Panihati, Sodepur, Kolkata-700114 his support and assistance in the preparation of this review article. This work in also supported by Guru Nanak Institute of Pharmaceutical Science and Technology. We acknowledge the contributions of all individuals who have directly or indirectly contributed to the completion of this manuscript. Thank you for the opportunity to submit this review article to International Journal of Pharmaceutical Sciences and Research. We are grateful for the consideration given to our work.

CONFLICT OF INTEREST: The authors declare that they have no conflicts of interest relevant to this review article.

REFERENCES:

1. Mainville J, Lillo SD, Poirier N and Plante N: Schedule Evaluation Tool. Creating Visual Schedules [Internet]. 2024; 195–195.
2. World Health Organization. Quality assurance of pharmaceuticals: a compendium of guidelines and related materials. Volume 2. Good manufacturing practices and inspection. World Health Organization 2024; 31.
3. Shinde AA, Gurav AS, Chaudhari BP and Redasani VK: A Review on Pharmaceutical Regulatory Authority of India, USA, UK, Australia. AJRPS 2024; 14(3).
4. Rajput H and Raikwar MA: Regulatory Authority AndGoverment Policies. The Center for Drug Evaluation and Research Uses Different Requirements for the Three Main Drug Product 2024; 13(4): 1.
5. Madanayake SN, Manipura A, Thakuria R and Adassooriya NM: Opportunities and challenges in mechanochemical cocrys-tallization toward scaled-up pharmaceutical manufacturing. Organic Process Research & Development 2023; 27(3): 409-22.
6. Tracy T, Wu L, Liu X, Cheng S and Li X: 3D printing: Innovative solutions for patients and pharmaceutical industry. Intern J of Pharmaceutics 2023; 631: 122480.
7. Suamte L, Tirkey A, Barman J and Babu PJ: Various manufacturing methods and ideal properties of scaffolds for tissue engineering applications. Smart Materials in Manufacturing 2023; 1: 100011.
8. Mishra L and Kurmi BD: Cosmetics regulations and standardization guidelines. Pharmaspire 2023; 15: 137-50.
9. Patel KT and Chotai NP: GMP Requirements for" buildings and facilities" for api-comparison of schedule m, India and ICH guideline and approach for compliance to different regulatory expectations. PSM 2013; 4(1).
10. Pocatilu P and Vetrici M: Schedule risk management for business M-applications development projects. WSEAS Transactions on Computers 2009; 8(4): 735-45.
11. Mishra L and Kurmi BD: Cosmetics regulations and standardization guidelines. Pharmaspire 2023; 15: 137-50.
12. Biswal S:  Drugs and cosmetics act, 1940 and interpretation of definitions. RJPLS 2020; 1(1): 1-9.
13. Weaver E, O’Hagan C and Lamprou DA: The sustainability of emerging technologies for use in pharmaceutical manufacturing. Expert Opinion on Drug Delivery 2022; 19(7): 861-72.
14. Becker J, Manske C and Randl S: Green chemistry and sustainability metrics in the pharmaceutical manufacturing sector. Current Opinion in Green and Sustainable Chemistry 2022; 33: 100562.
15. Souto EB, Silva GF, Dias-Ferreira J, Zielinska A, Ventura F, Durazzo A, Lucarini M, Novellino E and Santini A: Nanopharmaceutics: Part I—Clinical trials legislation and good manufacturing practices (GMP) of nanotherapeutics in the EU. Pharmaceutics 2020; 12(2): 146.
16. Ahmed S, Islam S, Ullah B, Biswas SK, Azad AS and Hossain S: A review article on pharmaceutical analysis of pharmaceutical industry according to pharmacopoeias. Oriental Journal of Chemistry 2020; 36(1).
17. Zothanpuii F, Rajesh R and Selvakumar KJ: A review on stability testing guidelines of pharmaceutical products. Asian J Pharm Clin Res 2020; 13(10): 3-9.
18. Barshikar R: Covid 19–Impact and new normal for pharmaceutical industry (Part–I). Journal of Generic Medicines 2020; 16(3): 112-9.
19. Kakad SB, Kolhe MH and Dukre TP: A review on pharmaceutical validation. International Journal of Pharmaceutical Quality Assurance 2020; 11(3): 338-42.
20. Wood JP: Containment in the pharmaceutical industry. CRC Press 2020; 26.
    

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    How to cite this article:

    Dey S, Dutta S and Ray J: A review article on an existing schedule m vs revised schedule M. Int J Pharm Sci & Res 2025; 16(3): 663-69. doi: 10.13040/IJPSR.0975-8232.16(3).663-69.

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